PMID- 21533221 OWN - NLM STAT- MEDLINE DCOM- 20110812 LR - 20211020 IS - 1553-7404 (Electronic) IS - 1553-7390 (Print) IS - 1553-7390 (Linking) VI - 7 IP - 4 DP - 2011 Apr TI - Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes. PG - e1001366 LID - 10.1371/journal.pgen.1001366 [doi] LID - e1001366 AB - In higher eukaryotes, messenger RNAs (mRNAs) are exported from the nucleus to the cytoplasm via factors deposited near the 5' end of the transcript during splicing. The signal sequence coding region (SSCR) can support an alternative mRNA export (ALREX) pathway that does not require splicing. However, most SSCR-containing genes also have introns, so the interplay between these export mechanisms remains unclear. Here we support a model in which the furthest upstream element in a given transcript, be it an intron or an ALREX-promoting SSCR, dictates the mRNA export pathway used. We also experimentally demonstrate that nuclear-encoded mitochondrial genes can use the ALREX pathway. Thus, ALREX can also be supported by nucleotide signals within mitochondrial-targeting sequence coding regions (MSCRs). Finally, we identified and experimentally verified novel motifs associated with the ALREX pathway that are shared by both SSCRs and MSCRs. Our results show strong correlation between 5' untranslated region (5'UTR) intron presence/absence and sequence features at the beginning of the coding region. They also suggest that genes encoding secretory and mitochondrial proteins share a common regulatory mechanism at the level of mRNA export. FAU - Cenik, Can AU - Cenik C AD - Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America. FAU - Chua, Hon Nian AU - Chua HN FAU - Zhang, Hui AU - Zhang H FAU - Tarnawsky, Stefan P AU - Tarnawsky SP FAU - Akef, Abdalla AU - Akef A FAU - Derti, Adnan AU - Derti A FAU - Tasan, Murat AU - Tasan M FAU - Moore, Melissa J AU - Moore MJ FAU - Palazzo, Alexander F AU - Palazzo AF FAU - Roth, Frederick P AU - Roth FP LA - eng GR - R01 HG001715/HG/NHGRI NIH HHS/United States GR - R21 MH087394/MH/NIMH NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - NS035611/NS/NINDS NIH HHS/United States GR - U01 HG001715/HG/NHGRI NIH HHS/United States GR - HG003224/HG/NHGRI NIH HHS/United States GR - U01 HL081341/HL/NHLBI NIH HHS/United States GR - U41 HG001715/HG/NHGRI NIH HHS/United States GR - HG004233/HG/NHGRI NIH HHS/United States GR - MH087394/MH/NIMH NIH HHS/United States GR - P01 NS035611/NS/NINDS NIH HHS/United States GR - HL081341/HL/NHLBI NIH HHS/United States GR - P50 HG004233/HG/NHGRI NIH HHS/United States GR - R01 HG003224/HG/NHGRI NIH HHS/United States GR - HG001715/HG/NHGRI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110414 PL - United States TA - PLoS Genet JT - PLoS genetics JID - 101239074 RN - 0 (5' Untranslated Regions) RN - 0 (Protein Sorting Signals) RN - 0 (RNA, Messenger) RN - JAC85A2161 (Adenine) SB - IM MH - 5' Untranslated Regions/*genetics MH - Active Transport, Cell Nucleus MH - Adenine/metabolism MH - *Alternative Splicing MH - Cell Nucleus/*metabolism MH - Cytoplasm MH - Endoplasmic Reticulum/genetics MH - Gene Expression Regulation MH - Genes, Mitochondrial MH - Humans MH - Introns MH - Models, Genetic MH - Open Reading Frames MH - Protein Sorting Signals MH - RNA Splicing MH - *RNA Transport MH - RNA, Messenger/*metabolism PMC - PMC3077370 COIS- The authors have declared that no competing interests exist. EDAT- 2011/05/03 06:00 MHDA- 2011/08/13 06:00 PMCR- 2011/04/01 CRDT- 2011/05/03 06:00 PHST- 2010/08/09 00:00 [received] PHST- 2011/03/07 00:00 [accepted] PHST- 2011/05/03 06:00 [entrez] PHST- 2011/05/03 06:00 [pubmed] PHST- 2011/08/13 06:00 [medline] PHST- 2011/04/01 00:00 [pmc-release] AID - 10-PLGE-RA-3857R2 [pii] AID - 10.1371/journal.pgen.1001366 [doi] PST - ppublish SO - PLoS Genet. 2011 Apr;7(4):e1001366. doi: 10.1371/journal.pgen.1001366. Epub 2011 Apr 14.