title: Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes.
abstract: 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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Can
authors.initials: C
authors.lastname: Cenik
authors.forename: Hon Nian
authors.initials: HN
authors.lastname: Chua
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Tarnawsky
authors.forename: Abdalla
authors.initials: A
authors.lastname: Akef
authors.forename: Adnan
authors.initials: A
authors.lastname: Derti
authors.forename: Murat
authors.initials: M
authors.lastname: Tasan
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Palazzo
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D021581:Active Transport, Cell Nucleus; D000225:Adenine / Q000378:metabolism; D017398:Alternative Splicing; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm; D004721:Endoplasmic Reticulum / Q000235:genetics; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D016366:Open Reading Frames; D021382:Protein Sorting Signals; D012326:RNA Splicing; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D000225:Adenine