Major splice variants and multiple polyadenylation site utilization in mRNAs encoding human translation initiation factors eIF4E1 and eIF4E3 regulate the translational regulators?
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
NT13713-4
Ministry of Health of the Czech Republic
GBP305/12/G034
Czech Science Foundation
PubMed
28942592
DOI
10.1007/s00438-017-1375-4
PII: 10.1007/s00438-017-1375-4
Knihovny.cz E-zdroje
- Klíčová slova
- 3′RACE, 4EHP, Alternative polyadenylation, Polyadenylation signal, Translation, eIF4E, eIF4E2, eIF4E3,
- MeSH
- 3' nepřekládaná oblast MeSH
- buněčné linie MeSH
- eukaryotický iniciační faktor 4E genetika metabolismus MeSH
- exprimované sekvenční adresy MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mozek metabolismus MeSH
- placenta metabolismus MeSH
- polyadenylace genetika MeSH
- proteiny vázající čepičku mRNA genetika MeSH
- regulace genové exprese MeSH
- sestřih RNA genetika MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 3' nepřekládaná oblast MeSH
- EIF4E2 protein, human MeSH Prohlížeč
- eIF4E3 protein, human MeSH Prohlížeč
- eukaryotický iniciační faktor 4E MeSH
- messenger RNA MeSH
- proteiny vázající čepičku mRNA MeSH
Alternative polyadenylation is an important and pervasive mechanism that generates heterogeneous 3'-termini of mRNA and is considered an important regulator of gene expression. We performed bioinformatics analyses of ESTs and the 3'-UTRs of the main transcript splice variants of the translational initiation factor eIF4E1 and its family members, eIF4E2 and eIF4E3. This systematic analysis led to the prediction of new polyadenylation signals. All identified polyadenylation sites were subsequently verified by 3'RACE of transcripts isolated from human lymphoblastic cell lines. This led to the observation that multiple simultaneous polyadenylation site utilization occurs in single cell population. Importantly, we described the use of new polyadenylation site in the eIF4E1 mRNA, which lacked any known polyadenylation signal. The proportion of eIF4E1 transcripts derived from the first two polyadenylation sites in eIF4E1 mRNA achieved 15% in a wide range of cell lines. This result demonstrates the ubiquitous presence of ARE-lacking transcripts, which escape HuR/Auf1-mediated control, the main mechanism of eIF4E1 gene expression regulation. We found many EST clones documenting the significant production of transcript variants 2-4 of eIF4E2 gene that encode proteins with C-termini that were distinct from the mainly studied prototypical isoform A. Similarly, eIF4E3 mRNAs are produced as two main variants with the same very long 3'-UTR with potential for heavy post-transcriptional regulation. We identified sparsely documented transcript variant 1 of eIF4E3 gene in human placenta. eIF4E3 truncated transcript variants were found mainly in brain. We propose to elucidate the minor splice variants of eIF4E2 and eIF4E3 in great detail because they might produce proteins with modified features that fulfill different cellular roles from their major counterparts.
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