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.

The Y Chromosome Modulates Splicing and Sex-Biased Intron Retention Rates in Drosophila

“…We also observed a mild enrichment for sex-biased IR events in UTR regions ( Figure 2C) compared to the overall distribution. Intron retention in the 5'UTR could affect the export of mRNA from the nucleus (CENIK et al 2011) or its translation (REMY et al 2014), whereas intron retention in the 3'UTR could affect miRNA target sites (TAN et al 2007). The various roles of IR across genes and genomes are of interest for further research.…”

Introns in UTRs: Why we should stop ignoring them

“…2). In support of this model, nucleotide sequences near the 5 0 end of the ORF strongly correlate with 5UI status, and only sequences derived from 5UI-lacking transcripts can support mRNA export in the absence of splicing [30]. Although the ALREX sequence was first identified in ER-and mitochondrial-targeted genes, it can still function as a splicing-independent export element in other sequence contexts [30].…”

“…Unlike the canonical TREXdependent nuclear export pathway, the ALREX pathway does not require splicing [29]. Instead, ALREX facilitates mRNA export via a specific RNA sequence element located within the 5 0 end of the ORF [29,30]. This sequence element is particularly prominent in transcripts encoding ER and mitochondrial-targeted proteins, the same functional class that is depleted of 5UIs.…”

Identification of a Region within the Placental Alkaline Phosphatase mRNA That Mediates p180-dependent Targeting to the Endoplasmic Reticulum

“…ALPP-⌬TMD was made by removing nucleotides 1504 -1594 from the ALPP construct using restriction-free cloning. H1B-GFP and M1-ftz were described previously (7,13).…”

“…4D). In contrast, M1-ftz mRNA, which encodes a cytosolic protein and contains the mRNA nuclear export-promoting element M1 (13), was present predominantly in the cytoplasmic fraction (Fig. 4D).…”