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November 25, 1988, Vol 260, No. 20 >
ARTICLE | November 25, 1988

RNA Splicing and Genes FREE

Phillip A. Sharp, PhD
[+] Author Affiliations

Based on a lecture given at the presentation of the Albert Lasker Basic Medical Research Award, New York, Nov 18, 1988.

Reprints not available.


JAMA. 1988;260(20):3035-3041. doi:10.1001/jama.1988.03410200091032
Text Size: A A A
Published online
Article
References

The splicing of long transcripts of RNA (copied from DNA in the cell nucleus) into smaller, specific mRNA (ready for export to the protein-producing machinery in the cytoplasm) is an important event in the regulation of gene expression in eukaryotic cells. The splicing reaction occurs as a late step in the nuclear pathway for synthesis of mRNAs. This pathway commences with initiation of transcription by RNA polymerase II and probably involves an integrated series of steps each dependent on previous events. Splicing of precursors to mRNAs involves the formation of a spliceosome complex containing the 5' and 3' splice sites. This complex contains the evolutionarily highly conserved small nuclear RNAs (snRNAs) U2, U4, U5, and U6. The most abundant snRNA, U1, is required to form the spliceosome and may be a part of the spliceosome. Analogues of these snRNAs have been identified in yeast. Assembly of the spliceosome probably involves the binding of a multi-snRNA complex containing U4, U5, and U6 snRNAs. Several observations suggest that the association of snRNAs in such complexes is quite dynamic. It is argued that the snRNAs in the spliceosome form a catalytic RNA structure that is responsible for the cleavage and ligation steps during splicing.

(JAMA 1988;260:3035-3041)

REFERENCES

1 +
Berget SM, Moore C, Sharp PA:  Spliced RNA segments at the 5′-terminus of late adenovirus 2 mRNA . Proc Natl Acad Sci USA 1977;;74:3171-3175.
2 +
Milhausen M, Nelson RG, Sather S, et al:  Identification of a small RNA containing the trypanosome spliced leader: A donor of shared 5′ sequences of trypanosomatid mRNAs? Cell 1984;;38:721-729.
3 +
De Lange T, Berkvens TM, Veerman HJG, et al:  Comparison of the genes coding for the common 5′ terminal sequence of messenger RNAs in three trypanosome species . Nucleic Acids Res 1984;;12:4431-4443.
4 +
Krause M, Hirsh D:  A trans-spliced leader sequence on actin mRNA in C elegans . Cell 1987;;49:753-761.
5 +
Darnell JE Jr:  Variety in the level of gene control in eukaryotic cells . Nature 1982;;297:365-371.
6 +
Padgett RA, Grabowski PJ, Konarska MM, et al:  Splicing of messenger RNA precursors . Annu Rev Biochem 1986;;55:1119-1150.
7 +
Dreyfuss G:  Structure and function of nuclear and cytoplasmic ribonucleoprotein particles . Annu Rev Cell Biol 1986;;2:459-498.
8 +
Whitelaw E, Proudfort N:  α-Thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3' end processing in the human α2 globin gene . EMBO J 1986;;5:2915-2922.
9 +
Weil PA, Luse DS, Segall J, et al:  Selective and accurate initiation of transcription at the Ad2 major late promoter in a soluble system dependent on purified RNA polymerase II and DNA . Cell 1979;;18:469-484.
10 +
Manley JL, Fire A, Cano A, et al:  DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract . Proc Natl Acad Sci USA 1980;;77:3855-3859.
11 +
Birnstiel ML, Busslinger M, Strub K:  Transcription termination and 3′ processing: The end is in site! Cell 1985;;41:349-359.
12 +
Leff SE, Rosenfeld MG, Evans RM:  Complex transcription units: Diversity in gene expression by alternative RNA processing . Annu Rev Biochem 1986;;55:1091-1117.
13 +
Breitbart RE, Andreadis A, Nadal-Ginard B:  Alternative splicing: A ubiquitous mechanism for the generation of multiple protein isoforms from single genes . Annu Rev Biochem 1987;;56:467-495.
14 +
Sisodia SS, Sollner-Webb B, Cleveland DW:  Specificity of RNA maturation pathways: RNAs transcribed by RNA polymerase III are not substrates for splicing or polyadenylation . Mol Cell Biol 1987;;1:3602-3612.
15 +
Konarska MM, Padgett RA, Sharp PA:  Recognition of cap structure in splicing in vitro of mRNA precursors . Cell 1984;;38:731-736.
16 +
Choi YD, Grabowski PJ, Sharp PA, et al:  Inhibition of RNA splicing by an antibody to proteins of the pre-mRNA-ribonucleoprotein (hnRNP) particle . Science 1986;;231:1534-1539.
17 +
Skoglund U, Andersson K, Strandberg B, et al:  Three-dimensional structure of a specific pre-messenger RNP particle established by electron microscopetomography . Nature 1986;;319:560-564.
18 +
Beyer AL, Osheim YN:  Splice site selection, rate of splicing, and alternative splicing on nascent transcripts . Genes Dev 1988;;2:754-765.
19 +
Grabowski PJ, Padgett RA, Sharp PA:  Messenger RNA splicing in vitro: An excised intervening sequence and a potential intermediate . Cell 1984;;37:415-427.
20 +
Ruskin B, Krainer AR, Maniatis T, et al:  Excision of an intact intron as a novel lariat structure during premRNA splicing in vitro . Cell 1984;;38:317-331.
21 +
Konarska MM, Grabowski PJ, Padgett RA, et al:  Characterization of the branch site in lariat RNAs produced by splicing of mRNA precursors . Nature 1985;;313:552-557.
22 +
Cech TR, Zaug AJ, Grabowski PJ:  In vitro splicing of the ribosomal RNA precursor of Tetrahymena: Involvement of a guanosine nucleotide in the excision of the intervening sequence . Cell 1981;;27:487-496.
23 +
Cech TR, Bass BL:  Biological catalysis by RNA . Annu Rev Biochem 1986;;55:599-629.
24 +
Reed R, Maniatis T:  Intron sequences involved in lariat formation during pre-mRNA splicing . Cell 1985;;41:95-105.
25 +
Ruskin B, Greene JM, Green MR:  Cryptic branch point activation allows accurate in vitro splicing of human β-globin intron mutants . Cell 1985;;41:833-844.
26 +
Rodriguez JR, Pikielny CW, Rosbash M:  In vivo characterization of yeast mRNA processing intermediates . Cell 1984;;39:603-610.
27 +
Domdey H, Apostol B, Lin R-J, et al:  Lariat structures are in vivo intermediates in yeast pre-mRNA splicing . Cell 1984;;39:611-621.
28 +
Padgett RA, Konarska MM, Aebi M, et al:  Non-consensus branch-site sequences in the in vitro splicing of transcripts of mutant rabbit β-globin genes . Proc Natl Acad Sci USA 1985;;82:8349-8353.
29 +
Brody, E, Abelson J:  The 'spliceosome': Yeast premessenger RNA associates with a 40S complex in a splicing-dependent reaction . Science 1985;;228:963-967.
30 +
Grabowski PJ, Seiler SR, Sharp PA:  A multicomponent complex is involved in the splicing of messenger RNA precursors . Cell 1985;;42:345-353.
31 +
Frendewey D, Keller W:  Stepwise assembly of a pre-mRNA splicing complex requires U-snRNPs and specific intron sequences . Cell 1985;;42:355-367.
32 +
Zeitlin S, Efstratiadis A:  In vivo splicing products of the rabbit β-globin pre-mRNA . Cell 1984;;39:589-602.
33 +
Wallace JC, Edmonds M:  Polyadenylated nuclear RNA contains branches . Proc Natl Acad Sci USA 1983;;80:950-954.
34 +
Padgett RA, Hardy SF, Sharp PA:  Splicing of adenovirus RNA in a cell free transcription system . Proc Natl Acad Sci USA 1983;;80:5230-5234.
35 +
Hernandez N, Keller W:  Splicing of in vitro synthesized messenger RNA precursors in HeLa cell extracts . Cell 1983;;35:89-99.
36 +
Hardy SF, Grabowski PJ, Padgett RR, et al:  Co-factor requirements of splicing of purified messenger RNA precursors . Nature 1984;;308:375-377.
37 +
Perler F, Efstratiadis A, Lomedico P, et al:  The evolution of genes: The chicken preproinsulin gene . Cell 1980;;20:555-566.
38 +
Brinster RL, Allen JM, Behringer RR, et al:  Introns increase transcriptional efficiency in transgenic mice . Proc Natl Acad Sci USA 1988;;85:836-840.
39 +
Busch H, Reddy R, Rothblum L, et al:  snRNAs, snRNPs, and RNA processing . Annu Rev Biochem 1982;;51:617-654.
40 +
Lerner MR, Steitz JA:  Snurps and scyrps . Cell 1981;;25:298-300.
41 +
Lerner MR, Steitz JA:  Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus . Proc Natl Acad Sci USA 1979;;76:5495-5499.
42 +
Lerner MR, Boyle JA, Mount SM, et al:  Are snRNPs involved in splicing? Nature 1980;;283:220-224.
43 +
Rogers J, Wall R:  A mechanism for RNA splicing . Proc Natl Acad Sci USA 1980;;77:1877-1879.
44 +
Guthrie C, Patterson B:  Spliceosomal snRNAs . Annu Rev Genet , in press.
45 +
Kretzner L, Rymond BC, Rosbash M:  S cerevisiae Ul RNA is large and has limited primary sequence homology to metazoon Ul snRNA . Cell 1987;;50:593-602.
46 +
Siliciano PG, Jones MH, Guthrie C:  Saccharomyces cerevisiae has a Ul-like small nuclear RNA with unexpected properties . Science 1987;;237:1484-1487.
47 +
Zhuang Y, Weiner AM:  A compensatory base change in Ul snRNA suppresses a 5′ splice site mutation . Cell 1986;;46:827-835.
48 +
Parker R, Siliciano PG, Guthrie C:  Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA . Cell 1987;;49:229-239.
49 +
Konarska MM, Sharp PA:  Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs . Cell 1986;;46:845.
50 +
Konarska MM, Sharp PA:  Interactions between small nuclear ribonucleoprotein particles in formation of spliceosomes . Cell 1987;;49:763.
51 +
Lamond AI, Konarska MM, Grabowski PJ, et al:  Spliceosome assembly involves the binding and release of U4 snRNP . Proc Natl Acad Sci USA 1988;;85:411-415.
52 +
Pikielny CW, Rymond BC, Rosbash M:  Electrophoresis of ribonucleoproteins reveals an ordered assembly pathway of yeast splicing complexes . Nature 1986;;324:341-345.
53 +
Cheng S-C, Abelson J:  Spliceosome assembly in yeast . Genes Dev 1987;;1:1014-1027.
54 +
Pikielny CW, Rosbash M:  Specific small nuclear RNAs are associated with yeast spliceosomes . Cell 1986;;45:869-877.
55 +
Bindereif A, Green MR:  An ordered pathway of snRNP binding during mammalian pre-mRNA splicing complex assembly . EMBO J 1987;;6:2415-2424.
56 +
Zillmann M, Rose SD, Berget SM:  U1 small nuclear ribonucleoproteins are required early during spliceosome assembly . Mol Cell Biol 1987;;7:2877-2883.
57 +
Konarska MM, Sharp PA:  Association of U2, U4, U5, and U6 small nuclear ribonucleoproteins in a spliceosome-type complex in absence of precursor RNA . Proc Natl Acad Sci USA 1988;;85:5459-5462.
58 +
Hashimoto C, Steitz JA:  U4 and U6 RNAs coexist in a single small nuclear ribonucleoprotein particle . Nucleic Acids Res 1984;;12:3283-3293.
59 +
Bringmann P, Appel B, Rinke J, et al:  Evidence for the existence of snRNAs U4 and U6 in a single ribonucleoprotein complex and for their association by intermolecular base pairing . EMBO J 1984;;3:1357-1363.
60 +
Lossky M, Anderson GJ, Jackson SP, et al:  Identification of a yeast snRNP protein and detection of snRNP-snRNP interactions . Cell 1987;;51:1019-1026.
61 +
Lustig AJ, Lin R-J, Abelson J:  The yeast RNA gene products are essential for mRNA splicing in vitro . Cell 1986;;47:953-963.
62 +
Solnick D, Lee SI:  Amount of RNA secondary structure required to induce an alternative splice . Mol Cell Biol 1987;;7:3194-3198.
63 +
Eperon LP, Graham IR, Griffiths AD, et al:  Effects of RNA secondary structure on alternative splicing of pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase? Cell 1988;;54:393-401.
64 +
Chu G, Sharp PA:  A gene chimeare of SV40 and mouse β-globin is transcribed and properly spliced . Nature 1981;;289:378-382.
65 +
Swanson MS, Dreyfuss G:  Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities . Mol Cell Biol 1988;;8:2237-2241.
66 +
Swanson MS, Dreyfuss G:  Specific binding and ATP-dependent complex formation of hnRNP proteins at the 3' end of introns . EMBO J , in press.
67 +
Baker BS, Wolfner MF:  A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster . Genes Dev 1988;;2:477-489.
68 +
Maine EM, Salz HK, Schedl P, et al:  Sex-lethal, a link between sex determination and sexual differentiation in Drosophila melanogaster . Cold Spring Harbor Symp Quant Biol 1985;;50:595-604.
69 +
Bell LR, Maine EM, Schedle P, et al:  Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins . Cell , in press.
70 +
Peebles CL, Perlan PS, Mecklenburg KL, et al:  A self-splicing RNA excises an intron lariat . Cell 1986;;44:213-223.
71 +
Van der Veen R, Arnberg AC, van der Horst G, et al:  Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro . Cell 1986;;44:225-234.
72 +
Sharp PA:  On the origin of RNA splicing and introns . Cell 1985;;42:397-400.
73 +
Cech TR:  RNA splicing: Three themes with variations . Cell 1985;;43:713-716.
74 +
Noller HF:  Structure of ribosomal RNA . Annu Rev Biochem 1984;;53:119-162.
75 +
Nomura M:  The role of RNA and protein in ribosome function: A review of early reconstitution studies and prospects for future studies . Cold Spring Harbor Symp Quant Biol 1987;;52:653-664.
76 +
Crick FHC:  On the origins of translation . J Mol Biol 1968;;38:367-379.
77 +
Cech TR:  Self-splicing RNA: Implications for evolution . Int Rev Cytol 1985;;93:3-22.
78 +
Gilbert W:  The exon theory of genes . Cold Spring Harbor Symp Quant Biol 1987;;52:901-905.
79 +
Teem JL, Abovich N, Kaufer NF, et al:  A comparison of yeast ribosomal protein gene DNA sequences . Nucleic Acids Res 1984;;12:8295-8301.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Berget SM, Moore C, Sharp PA:  Spliced RNA segments at the 5′-terminus of late adenovirus 2 mRNA . Proc Natl Acad Sci USA 1977;;74:3171-3175.
2 +
Milhausen M, Nelson RG, Sather S, et al:  Identification of a small RNA containing the trypanosome spliced leader: A donor of shared 5′ sequences of trypanosomatid mRNAs? Cell 1984;;38:721-729.
3 +
De Lange T, Berkvens TM, Veerman HJG, et al:  Comparison of the genes coding for the common 5′ terminal sequence of messenger RNAs in three trypanosome species . Nucleic Acids Res 1984;;12:4431-4443.
4 +
Krause M, Hirsh D:  A trans-spliced leader sequence on actin mRNA in C elegans . Cell 1987;;49:753-761.
5 +
Darnell JE Jr:  Variety in the level of gene control in eukaryotic cells . Nature 1982;;297:365-371.
6 +
Padgett RA, Grabowski PJ, Konarska MM, et al:  Splicing of messenger RNA precursors . Annu Rev Biochem 1986;;55:1119-1150.
7 +
Dreyfuss G:  Structure and function of nuclear and cytoplasmic ribonucleoprotein particles . Annu Rev Cell Biol 1986;;2:459-498.
8 +
Whitelaw E, Proudfort N:  α-Thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3' end processing in the human α2 globin gene . EMBO J 1986;;5:2915-2922.
9 +
Weil PA, Luse DS, Segall J, et al:  Selective and accurate initiation of transcription at the Ad2 major late promoter in a soluble system dependent on purified RNA polymerase II and DNA . Cell 1979;;18:469-484.
10 +
Manley JL, Fire A, Cano A, et al:  DNA-dependent transcription of adenovirus genes in a soluble whole-cell extract . Proc Natl Acad Sci USA 1980;;77:3855-3859.
11 +
Birnstiel ML, Busslinger M, Strub K:  Transcription termination and 3′ processing: The end is in site! Cell 1985;;41:349-359.
12 +
Leff SE, Rosenfeld MG, Evans RM:  Complex transcription units: Diversity in gene expression by alternative RNA processing . Annu Rev Biochem 1986;;55:1091-1117.
13 +
Breitbart RE, Andreadis A, Nadal-Ginard B:  Alternative splicing: A ubiquitous mechanism for the generation of multiple protein isoforms from single genes . Annu Rev Biochem 1987;;56:467-495.
14 +
Sisodia SS, Sollner-Webb B, Cleveland DW:  Specificity of RNA maturation pathways: RNAs transcribed by RNA polymerase III are not substrates for splicing or polyadenylation . Mol Cell Biol 1987;;1:3602-3612.
15 +
Konarska MM, Padgett RA, Sharp PA:  Recognition of cap structure in splicing in vitro of mRNA precursors . Cell 1984;;38:731-736.
16 +
Choi YD, Grabowski PJ, Sharp PA, et al:  Inhibition of RNA splicing by an antibody to proteins of the pre-mRNA-ribonucleoprotein (hnRNP) particle . Science 1986;;231:1534-1539.
17 +
Skoglund U, Andersson K, Strandberg B, et al:  Three-dimensional structure of a specific pre-messenger RNP particle established by electron microscopetomography . Nature 1986;;319:560-564.
18 +
Beyer AL, Osheim YN:  Splice site selection, rate of splicing, and alternative splicing on nascent transcripts . Genes Dev 1988;;2:754-765.
19 +
Grabowski PJ, Padgett RA, Sharp PA:  Messenger RNA splicing in vitro: An excised intervening sequence and a potential intermediate . Cell 1984;;37:415-427.
20 +
Ruskin B, Krainer AR, Maniatis T, et al:  Excision of an intact intron as a novel lariat structure during premRNA splicing in vitro . Cell 1984;;38:317-331.
21 +
Konarska MM, Grabowski PJ, Padgett RA, et al:  Characterization of the branch site in lariat RNAs produced by splicing of mRNA precursors . Nature 1985;;313:552-557.
22 +
Cech TR, Zaug AJ, Grabowski PJ:  In vitro splicing of the ribosomal RNA precursor of Tetrahymena: Involvement of a guanosine nucleotide in the excision of the intervening sequence . Cell 1981;;27:487-496.
23 +
Cech TR, Bass BL:  Biological catalysis by RNA . Annu Rev Biochem 1986;;55:599-629.
24 +
Reed R, Maniatis T:  Intron sequences involved in lariat formation during pre-mRNA splicing . Cell 1985;;41:95-105.
25 +
Ruskin B, Greene JM, Green MR:  Cryptic branch point activation allows accurate in vitro splicing of human β-globin intron mutants . Cell 1985;;41:833-844.
26 +
Rodriguez JR, Pikielny CW, Rosbash M:  In vivo characterization of yeast mRNA processing intermediates . Cell 1984;;39:603-610.
27 +
Domdey H, Apostol B, Lin R-J, et al:  Lariat structures are in vivo intermediates in yeast pre-mRNA splicing . Cell 1984;;39:611-621.
28 +
Padgett RA, Konarska MM, Aebi M, et al:  Non-consensus branch-site sequences in the in vitro splicing of transcripts of mutant rabbit β-globin genes . Proc Natl Acad Sci USA 1985;;82:8349-8353.
29 +
Brody, E, Abelson J:  The 'spliceosome': Yeast premessenger RNA associates with a 40S complex in a splicing-dependent reaction . Science 1985;;228:963-967.
30 +
Grabowski PJ, Seiler SR, Sharp PA:  A multicomponent complex is involved in the splicing of messenger RNA precursors . Cell 1985;;42:345-353.
31 +
Frendewey D, Keller W:  Stepwise assembly of a pre-mRNA splicing complex requires U-snRNPs and specific intron sequences . Cell 1985;;42:355-367.
32 +
Zeitlin S, Efstratiadis A:  In vivo splicing products of the rabbit β-globin pre-mRNA . Cell 1984;;39:589-602.
33 +
Wallace JC, Edmonds M:  Polyadenylated nuclear RNA contains branches . Proc Natl Acad Sci USA 1983;;80:950-954.
34 +
Padgett RA, Hardy SF, Sharp PA:  Splicing of adenovirus RNA in a cell free transcription system . Proc Natl Acad Sci USA 1983;;80:5230-5234.
35 +
Hernandez N, Keller W:  Splicing of in vitro synthesized messenger RNA precursors in HeLa cell extracts . Cell 1983;;35:89-99.
36 +
Hardy SF, Grabowski PJ, Padgett RR, et al:  Co-factor requirements of splicing of purified messenger RNA precursors . Nature 1984;;308:375-377.
37 +
Perler F, Efstratiadis A, Lomedico P, et al:  The evolution of genes: The chicken preproinsulin gene . Cell 1980;;20:555-566.
38 +
Brinster RL, Allen JM, Behringer RR, et al:  Introns increase transcriptional efficiency in transgenic mice . Proc Natl Acad Sci USA 1988;;85:836-840.
39 +
Busch H, Reddy R, Rothblum L, et al:  snRNAs, snRNPs, and RNA processing . Annu Rev Biochem 1982;;51:617-654.
40 +
Lerner MR, Steitz JA:  Snurps and scyrps . Cell 1981;;25:298-300.
41 +
Lerner MR, Steitz JA:  Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus . Proc Natl Acad Sci USA 1979;;76:5495-5499.
42 +
Lerner MR, Boyle JA, Mount SM, et al:  Are snRNPs involved in splicing? Nature 1980;;283:220-224.
43 +
Rogers J, Wall R:  A mechanism for RNA splicing . Proc Natl Acad Sci USA 1980;;77:1877-1879.
44 +
Guthrie C, Patterson B:  Spliceosomal snRNAs . Annu Rev Genet , in press.
45 +
Kretzner L, Rymond BC, Rosbash M:  S cerevisiae Ul RNA is large and has limited primary sequence homology to metazoon Ul snRNA . Cell 1987;;50:593-602.
46 +
Siliciano PG, Jones MH, Guthrie C:  Saccharomyces cerevisiae has a Ul-like small nuclear RNA with unexpected properties . Science 1987;;237:1484-1487.
47 +
Zhuang Y, Weiner AM:  A compensatory base change in Ul snRNA suppresses a 5′ splice site mutation . Cell 1986;;46:827-835.
48 +
Parker R, Siliciano PG, Guthrie C:  Recognition of the TACTAAC box during mRNA splicing in yeast involves base pairing to the U2-like snRNA . Cell 1987;;49:229-239.
49 +
Konarska MM, Sharp PA:  Electrophoretic separation of complexes involved in the splicing of precursors to mRNAs . Cell 1986;;46:845.
50 +
Konarska MM, Sharp PA:  Interactions between small nuclear ribonucleoprotein particles in formation of spliceosomes . Cell 1987;;49:763.
51 +
Lamond AI, Konarska MM, Grabowski PJ, et al:  Spliceosome assembly involves the binding and release of U4 snRNP . Proc Natl Acad Sci USA 1988;;85:411-415.
52 +
Pikielny CW, Rymond BC, Rosbash M:  Electrophoresis of ribonucleoproteins reveals an ordered assembly pathway of yeast splicing complexes . Nature 1986;;324:341-345.
53 +
Cheng S-C, Abelson J:  Spliceosome assembly in yeast . Genes Dev 1987;;1:1014-1027.
54 +
Pikielny CW, Rosbash M:  Specific small nuclear RNAs are associated with yeast spliceosomes . Cell 1986;;45:869-877.
55 +
Bindereif A, Green MR:  An ordered pathway of snRNP binding during mammalian pre-mRNA splicing complex assembly . EMBO J 1987;;6:2415-2424.
56 +
Zillmann M, Rose SD, Berget SM:  U1 small nuclear ribonucleoproteins are required early during spliceosome assembly . Mol Cell Biol 1987;;7:2877-2883.
57 +
Konarska MM, Sharp PA:  Association of U2, U4, U5, and U6 small nuclear ribonucleoproteins in a spliceosome-type complex in absence of precursor RNA . Proc Natl Acad Sci USA 1988;;85:5459-5462.
58 +
Hashimoto C, Steitz JA:  U4 and U6 RNAs coexist in a single small nuclear ribonucleoprotein particle . Nucleic Acids Res 1984;;12:3283-3293.
59 +
Bringmann P, Appel B, Rinke J, et al:  Evidence for the existence of snRNAs U4 and U6 in a single ribonucleoprotein complex and for their association by intermolecular base pairing . EMBO J 1984;;3:1357-1363.
60 +
Lossky M, Anderson GJ, Jackson SP, et al:  Identification of a yeast snRNP protein and detection of snRNP-snRNP interactions . Cell 1987;;51:1019-1026.
61 +
Lustig AJ, Lin R-J, Abelson J:  The yeast RNA gene products are essential for mRNA splicing in vitro . Cell 1986;;47:953-963.
62 +
Solnick D, Lee SI:  Amount of RNA secondary structure required to induce an alternative splice . Mol Cell Biol 1987;;7:3194-3198.
63 +
Eperon LP, Graham IR, Griffiths AD, et al:  Effects of RNA secondary structure on alternative splicing of pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase? Cell 1988;;54:393-401.
64 +
Chu G, Sharp PA:  A gene chimeare of SV40 and mouse β-globin is transcribed and properly spliced . Nature 1981;;289:378-382.
65 +
Swanson MS, Dreyfuss G:  Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities . Mol Cell Biol 1988;;8:2237-2241.
66 +
Swanson MS, Dreyfuss G:  Specific binding and ATP-dependent complex formation of hnRNP proteins at the 3' end of introns . EMBO J , in press.
67 +
Baker BS, Wolfner MF:  A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster . Genes Dev 1988;;2:477-489.
68 +
Maine EM, Salz HK, Schedl P, et al:  Sex-lethal, a link between sex determination and sexual differentiation in Drosophila melanogaster . Cold Spring Harbor Symp Quant Biol 1985;;50:595-604.
69 +
Bell LR, Maine EM, Schedle P, et al:  Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins . Cell , in press.
70 +
Peebles CL, Perlan PS, Mecklenburg KL, et al:  A self-splicing RNA excises an intron lariat . Cell 1986;;44:213-223.
71 +
Van der Veen R, Arnberg AC, van der Horst G, et al:  Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro . Cell 1986;;44:225-234.
72 +
Sharp PA:  On the origin of RNA splicing and introns . Cell 1985;;42:397-400.
73 +
Cech TR:  RNA splicing: Three themes with variations . Cell 1985;;43:713-716.
74 +
Noller HF:  Structure of ribosomal RNA . Annu Rev Biochem 1984;;53:119-162.
75 +
Nomura M:  The role of RNA and protein in ribosome function: A review of early reconstitution studies and prospects for future studies . Cold Spring Harbor Symp Quant Biol 1987;;52:653-664.
76 +
Crick FHC:  On the origins of translation . J Mol Biol 1968;;38:367-379.
77 +
Cech TR:  Self-splicing RNA: Implications for evolution . Int Rev Cytol 1985;;93:3-22.
78 +
Gilbert W:  The exon theory of genes . Cold Spring Harbor Symp Quant Biol 1987;;52:901-905.
79 +
Teem JL, Abovich N, Kaufer NF, et al:  A comparison of yeast ribosomal protein gene DNA sequences . Nucleic Acids Res 1984;;12:8295-8301.

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To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
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