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Cited by 19RNA Research and SplicingRNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancer

eIF4G2 balances its own mRNA translation via a PCBP2-based feedback loop

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Smirnova, Victoria V., Shestakova, Ekaterina D., Bikmetov, Dmitry V., Chugunova, Anastasia A., Osterman, Ilya A., Serebryakova, Marina V., Sergeeva, Olga V., Zatsepin, Timofey S. +2 more·2019·RNA
DOI 10.1261/rna.065623.118PMC PMC6573783
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Abstract

Poly(rC)-binding protein 2 (PCBP2, hnRNP E2) is one of the most abundant RNA-binding proteins in mammalian cells. In humans, it exists in seven isoforms, which are assumed to play similar roles in cells. The protein is shown to bind 3′-untranslated regions (3′-UTRs) of many mRNAs and regulate their translation and/or stability, but nothing is known about the functional consequences of PCBP2 binding to 5′-UTRs. Here we show that the PCBP2 isoform f interacts with the 5′-UTRs of mRNAs encoding eIF4G2 (a translation initiation factor with a yet unknown mechanism of action, also known as DAP5) and Cyclin I, and inhibits their translation in vitro and in cultured cells, while the PCBP2 isoform e only affects Cyclin I translation. Furthermore, eIF4G2 participates in a cap-dependent translation of the PCBP2 mRNA. Thus, PCBP2 and eIF4G2 seem to regulate one another's expression via a novel type of feedback loop formed by the translation initiation factor and the RNA-binding protein.

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  • The direction of the influence of an RBP on the stability and translation efficiency of RNA can depend on the cell type and on the target RNA, as exemplified by PCBP2.

    “Nevertheless, it should be noted that the direction of the influence of an RBP on the stability and translation efficiency of RNA can depend on the cell type and on the target RNA, as exemplified by PCBP2: it can stabilize some mRNAs but promotes the degradation of other mRNAs [25,26,27].”

    From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [25]

    The Introduction says poly(rC)-binding proteins can stabilize or destabilize mRNAs, and the Conclusions show that PCBP2’s effects on translation differ by isoform and target RNA. But the paper does not establish that PCBP2 itself stabilizes some mRNAs and promotes degradation of others, or that the direction of its effect reverses by cell type. Its Results and Discussion instead report no significant stability differences among the reporters tested in Huh7 or 293T cells. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Smirnova, V. V., Shestakova, E. D., Bikmetov, D. V., Chugunova, A. A., Osterman, I. A., Serebryakova, M. V., Sergeeva, O. V., Zatsepin, T. S., Shatsky, I. N., & Terenin, I. M.
Affiliations
  • Lomonosov Moscow State University (RU)
  • Skolkovo Institute of Science and Technology (RU)
  • Sechenov University (RU)
ORCID
Venue
RNA
Publisher
Cold Spring Harbor Laboratory
Published
2019-04-22
Volume
25
Issue
7
Pages
757-767
ISSN
  • 1355-8382 (ISSN-L)
  • 1469-9001
DOI
10.1261/rna.065623.118
PMC
PMC6573783
OpenAlex
W2942188614
Cited by
19
References
0
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 1
FWCI
0.74
Type
journal article
Language
en
Open access
Locations
  • RNA (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Russian Science Foundation (19-14-00152)
  • Russian Foundation for Basic Research (16-04-01628)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
eIF4G2, PCBP2, feedback loops, mRNA translation regulation, 5' untranslated region, 3' untranslated region, RNA-binding proteins, translation initiation factors, cap-dependent translation, D-AP5
MeSH terms
Cells, Cultured, Humans, RNA, Messenger, Protein Biosynthesis, RNA-Binding Proteins, 5' Untranslated Regions, Eukaryotic Initiation Factor-4G

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