Search

Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs. To explore this possibility, we searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE and each regulated by SMD, by measuring changes in mRNA abundance after individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'-UTR SINEs that independently function in SMD control of myoblast metabolism. Expanding to other species, we demonstrated that SINE-directed SMD likely emerged in both primate and rodent lineages >20-25 million years ago. Our work reveals a mechanism for the convergent evolution of posttranscriptional gene regulatory networks in mammals by species-specific SINE transposition and SMD.

Staufen 1 (STAU1)-mediated messenger RNA decay (SMD) involves the degradation of translationally active mRNAs whose 3'-untranslated regions (3' UTRs) bind to STAU1, a protein that binds to double-stranded RNA (1,2). Earlier studies defined the STAU1-binding site within ADP-ribosylation factor 1 (ARF1)mRNAasa 19-base-pair stem with a 100-nucleotide apex (2). However, we were unable to identify comparable structures in the 3' UTRs of other targets of SMD. Here we show that STAU1-binding sites can be formed by imperfect base-pairing between an Alu element in the 3' UTR of an SMD target and another Alu element in a cytoplasmic, polyadenylated long non-coding RNA (lncRNA). An individual lncRNA can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions of non-coding RNAs and Alu elements (3-5). Not all mRNAs that contain an Alu element in the 3' UTR are targeted for SMD even in the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known transacting RNA effectors consist of fewer than 200 nucleotides, and these include small nucleolar RNAs and microRNAs. Our finding that the binding of STAU1 to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy that cells use to recruit proteins to mRNAs and mediate the decay of these mRNAs. We name these lncRNAs half-STAU1-binding site RNAs (1/2-sbsRNAs)., Using the program mfold (6), we failed to identify double-stranded RNA (dsRNA) structures similar to the STAU1-binding site (SBS) of ARF1 mRNA in the 3' UTRs of other SMD targets. [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.07.022 Byline: Lynne E. Maquat (1), Woan-Yuh Tarn (1)(3), Olaf Isken (2) Abstract: In mammalian cells, newly synthesized mRNAs undergo a pioneer round of translation that is important for mRNA quality control. Following maturation of messenger ribonucleoprotein particles during and after the pioneer round, steady-state cycles of mRNA translation generate most of the cell's proteins. Translation factors, RNA-binding proteins, and targets of signaling pathways that are particular to newly synthesized mRNAs regulate critical functions of the pioneer round. Author Affiliation: (1) Department of Biochemistry and Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA (2) Institute for Virology and Cell Biology, University of Lubeck, 23562 Lubeck, Germany (3) Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tibs.2009.05.003 Byline: Daniel R. Schoenberg (1), Lynne E. Maquat (2) Abstract: The 5'-cap structure that typifies all polymerase II-transcribed RNAs plays important roles in pre-mRNA processing and mRNA export, translation and quality control. Removal of the cap is a regulated process that is considered to be the first irreversible step in mRNA decay. An emerging view challenges this idea: mRNAs have been identified in mammalian cells that lack sequences from their 5' ends but nevertheless appear to be modified with a cap or cap-like structure. Furthermore, a cytoplasmic form of capping enzyme was recently identified that, together with a novel kinase, generates capped ends from cleaved RNAs. These and other findings provide evidence for re-capping and its possible functions. Author Affiliation: (1) Department of Molecular and Cellular Biochemistry and Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA (2) Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester, Rochester, NY 14642, USA

Previous work showed that human [beta]-globin mRNAs harboring a premature termination codon are degraded in the erythroid tissues of mice to products that lack sequences from the mRNA 5' end but contain a 5' cap-like structure. Whether these decay products are the consequence of endonucleolytic or 5'-to-3' exonucleolytic activity is unclear. We report that this [beta]-globin mRNA decay pathway is recapitulated in cultured mouse erythroleukemia (MEL) cells and targets nonsense-free mRNA to a lesser extent than nonsense-containing mRNA. S1 nuclease mapping and primer extension demonstrated that 70-80% of decay product 5' ends contain a UG dinucleotide. Detection of upstream counterparts of these decay products indicates that they are generated by endonucleolytic activity. Both crude and partially purified polysome extracts prepared from MEL cells contain an endonucleolytic activity that generates decay products comparable to those observed in vivo. These data suggest that an endonuclease with preference for UG dinucleotides is involved in the degradation of nonsense-containing and, to a lesser extent, nonsense-free human [beta]-globin mRNAs in mouse erythroid cells. nonsense codon | UG dinucleotides | mRNA endonuclease | polysomes

The author discusses the publications on fibrillin transcript. The topics of interest include the role of nonsense codon in the splice site choice and the effect of fibrillin transcript on exonic splicing enhancer.

Messenger RNA elimination occurs through nonsense-mediated decay in association with the nuclear cap binding protein, CBP80. Results show that CBP80-bound mRNA undergoes a round of translation before CBP80-CBP20 are rplaced by the cytoplasmic counterpart of CBP80, elF4E.

The authors present a review of the publications on the eukaryotic cellular proteins generated by the mRNA translation. The points of interest include gene transcription, pre-mRNA synthesis and processing, mRNA export and translation and response to dsRNA.