Autoregulation of the mRNA export factor Yra1p requires inefficient splicing of its pre-mRNA

RNA - Tập 12 Số 6 - Trang 994-1006 - 2006
Pascal J. Preker1, Christine Guthrie1
1Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-2020, USA

Tóm tắt

Yra1p is an essential RNA-binding protein that couples transcription to export. The YRA1 gene is one of only ∼5% of genes that undergo splicing in budding yeast, and its intron is unusual in several respects, including its large size and anomalous branchpoint sequence. We showed previously that the intron is required for autogenous regulation of Yra1p levels, which cause a dominant negative growth phenotype when elevated. The mechanism of this regulation, however, remains unknown. Here we demonstrate that growth is inversely correlated with splicing efficiency. Substitution of a canonical branchpoint moderately improves splicing but compromises autoregulation. Shortening the intron from 766 to ∼350 nt significantly improves splicing but abolishes autoregulation. Notably, proper regulation can be restored by insertion of unrelated sequences into the shortened intron. In that the current paradigm for regulated splicing involves the binding of protein factors to specific elements in the pre-mRNA, the regulation of YRA1 expression appears to occur by a novel mechanism. We propose that appropriate levels of Yra1p are maintained by inefficient cotranscriptional splicing.

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Tài liệu tham khảo

10.1038/sj.emboj.7600261

10.1038/nsmb0905-737

10.1006/jmbi.1990.9999

10.1146/annurev.biochem.72.121801.161720

10.1093/nar/gkg213

10.1146/annurev.genet.36.043002.091635

10.1016/0378-1119(92)90454-W

10.1016/0968-0004(89)90167-9

10.1016/0092-8674(91)90387-E

10.1016/0092-8674(91)90047-3

10.1002/yea.320110104

Fewell, 1999, Ribosomal protein S14 of Saccharomyces cerevisiae regulates its expression by binding to RPS14B pre-mRNA and to 18S rRNA, Mol. Cell. Biol., 19, 826, 10.1128/MCB.19.1.826

Guthrie C. Fink G.R. (2002) Guide to yeast genetics and molecular and cell biology (Academic Press, San Diego, CA).

10.1016/S1097-2765(03)00488-X

10.1261/rna.5390803

10.1016/j.molcel.2003.08.010

10.1016/S0960-9822(01)00529-2

10.1093/emboj/cdf335

10.1002/yea.1185

10.1038/sj.emboj.7600053

10.1101/gad.851301

10.1101/gad.1032902

10.1101/gad.892401

Libri, 1995, RNA structural patterns and splicing: Molecular basis for an RNA-based enhancer, RNA, 1, 425

10.1101/gad.852101

10.1128/MCB.22.23.8254-8266.2002

10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U

Lopez, 2000, Uncoupling yeast intron recognition from transcription with recursive splicing, EMBO Rep., 1, 334, 10.1093/embo-reports/kvd065

Nandabalan, 1995, Binding of a cell-type-specific RNA splicing factor to its target regulatory sequence, Mol. Cell. Biol., 15, 1953, 10.1128/MCB.15.4.1953

Newman, 1987, Specific accessory sequences in Saccharomyces cerevisiae introns control assembly of pre-mRNAs into spliceosomes, EMBO J., 6, 3833, 10.1002/j.1460-2075.1987.tb02720.x

Portman, 1997, YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein with RNA annealing activity, RNA, 3, 527

10.1017/S1355838202020046

10.1093/embo-reports/kvf091

10.1093/emboj/19.8.1873

10.1016/S0014-5793(00)02272-9

10.1016/S1097-2765(00)00033-2

10.1017/S1355838299981682

10.1093/emboj/19.3.410

10.1038/35098113

10.1038/nature746

10.1017/S1355838200000078

10.1017/S135583820000145X

10.1016/S1097-2765(00)80369-X

10.1128/MCB.23.20.7339-7349.2003

10.1128/MCB.22.23.8241-8253.2002

10.1101/gad.851701

10.1093/nar/gkg595

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RNA

Tập 12 Số 6

994-1006

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