Journal Article

Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes

Palazzo, Alexander F, Zhang, Hui, Tarnawsky, Stefan P, Derti, Adnan, Cenik, Can, Tasan, Murat, Chua, Hon Nian, Roth, Frederick P, Akef, Abdalla, Moore, Melissa J

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 5' Untranslated Regions - genetics / Active Transport, Cell Nucleus / Adenine - metabolism / Alternative Splicing / Cell Nucleus - metabolism / Cytoplasm / Endoplasmic Reticulum - genetics / Experiments / Exports / Gene Expression Regulation / Genes / Genes, Mitochondrial / Genetics / Genomes / Genomics / Humans / Hypothesis testing / Introns / Kinases / Medical research / Messenger RNA / Models, Genetic / Nucleotide sequence / Open Reading Frames / Physiological aspects / Protein Sorting Signals / RNA Splicing / RNA Transport / RNA, Messenger - metabolism