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

RNA
Pascal J Preker, C Guthrie

Abstract

Yra1p is an essential RNA-binding protein that couples transcription to export. The YRA1 gene is one of only approximately 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 approximately 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.

References

Jan 2, 1992·Gene·T W ChristiansonP Hieter
Sep 20, 1991·Cell·J A EngebrechtG S Roeder
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Apr 1, 1995·Molecular and Cellular Biology·K Nandabalan, G S Roeder
Apr 25, 2000·The EMBO Journal·B Rutz, B Séraphin
Jan 6, 2001·RNA·J VilardellJ R Warner
Jan 13, 2001·Genes & Development·D LibriJ Boulay
Jul 19, 2001·Genes & Development·E P LeiP A Silver
Nov 7, 2001·Current Biology : CB·T H JensenD Libri
Nov 5, 2002·Genes & Development·Elissa P Lei, Pamela A Silver
Nov 6, 2002·Molecular and Cellular Biology·Domenico LibriTorben Heick Jensen
Nov 14, 2002·Annual Review of Genetics·David A Brow
Feb 13, 2003·Nucleic Acids Research·Elisabeth BonClaude Gaillardin
Mar 11, 2003·Annual Review of Biochemistry·Douglas L Black
Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Oct 1, 2003·Molecular and Cellular Biology·Qiang Wang, Brian C Rymond
Dec 24, 2003·Molecular Cell·Patricia J Hilleren, Roy Parker
Jan 24, 2004·The EMBO Journal·Minkyu KimStephen Buratowski
Jun 12, 2004·The EMBO Journal·Katharine Compton AbruzziMichael Rosbash
Dec 8, 2004·Yeast·Arun K KashyapDouglas R Kellogg
Sep 6, 2005·Nature Structural & Molecular Biology·Andrés Aguilera

❮ Previous
Next ❯

Citations

Oct 30, 2014·Nucleic Acids Research·Marie Mi BondeAttila Becskei
Jun 21, 2007·Nucleic Acids Research·Emanuele BurattiFrancisco E Baralle
Feb 22, 2008·Molecular Biology of the Cell·Julie ParenteauSherif Abou Elela
Jul 14, 2011·Nucleic Acids Research·Munshi Azad HossainTracy L Johnson
Jul 14, 2011·Nucleic Acids Research·Bernardo Cuenca-BonoSusana Rodríguez-Navarro
Mar 1, 2012·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Philomène KabranCécile Neuvéglise
Nov 9, 2011·Molecular Genetics and Genomics : MGG·Zhi Cheng, Thomas M Menees
Mar 13, 2009·Briefings in Functional Genomics & Proteomics·Markus Meyer, Josep Vilardell
Jan 5, 2016·Nature Reviews. Molecular Cell Biology·Cornelia KilchertLidia Vasiljeva
Aug 9, 2011·Comptes rendus biologies·Cécile NeuvégliseClaude Gaillardin
Dec 5, 2009·Trends in Biochemical Sciences·M Bryan Warf, J Andrew Berglund
Mar 30, 2016·Cell·Fernando Carrillo OesterreichKarla M Neugebauer
Jan 18, 2012·Biochimica Et Biophysica Acta·Tracy L Johnson, Josep Vilardell
Sep 25, 2007·Molecular Cell·Jeffrey A PleissChristine Guthrie
Aug 12, 2008·Molecular Cell·Shakir SayaniGuillaume F Chanfreau
Jun 24, 2008·Molecular Cell·Sara MacíasJosep Vilardell
Mar 22, 2013·Applied Microbiology and Biotechnology·Frank Kempken
Jun 4, 2019·Journal of Molecular Cell Biology·Michaela Müller-McNicollJan Medenbach
Nov 1, 2021·FEMS Microbiology Letters·Suraya MuzafarRajendra Prasad
Nov 8, 2015·RNA·Ali AbuQattamSusana Rodríguez-Navarro

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.