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PreprintCited by 29RNA Research and SplicingRNA and protein synthesis mechanismsPI3K/AKT/mTOR signaling in cancer

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RNA binding protein PRRC2B mediates translation of specific mRNAs and regulates cell cycle progression

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Jiang, Feng, Hedaya, Omar M., Khor, EngSoon, Wu, Jiangbin, Auguste, Matthew, Yao, Peng·2022·Nucleic Acids Research
DOI 10.1101/2022.12.16.520836PMC PMC10287950

Preprint — published as 10.1093/nar/gkad322 · Paper page

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Abstract

Accumulating evidence suggests that posttranscriptional control of gene expression, including RNA splicing, transport, modification, translation, and degradation, primarily relies on RNA binding proteins (RBPs). However, the functions of many RBPs remain understudied. Here, we characterized the function of a novel RBP, Proline-Rich Coiled-coil 2B (PRRC2B). Through photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation and sequencing (PAR-CLIP-seq), we identified transcriptome-wide CU- or GA-rich PRRC2B binding sites near the translation initiation codon on a specific cohort of mRNAs in HEK293T cells. These mRNAs, including oncogenes and cell cycle regulators such as CCND2 (cyclin D2), exhibited decreased translation upon PRRC2B knockdown as revealed by polysome-associated RNA-seq, resulting in reduced G1/S phase transition and cell proliferation. Antisense oligonucleotides blocking PRRC2B interactions with CCND2 mRNA decreased its translation, thus inhibiting G1/S transition and cell proliferation. Mechanistically, PRRC2B interactome analysis revealed RNA-independent interactions with eukaryotic translation initiation factors 3 (eIF3) and 4G2 (eIF4G2). The interaction with translation initiation factors is essential for PRRC2B function since the eIF3/eIF4G2-interacting defective mutant, unlike wild-type PRRC2B, failed to rescue the translation deficiency or cell proliferation inhibition caused by PRRC2B knockdown. Altogether, our findings reveal that PRRC2B is essential for efficiently translating specific proteins required for cell cycle progression and cell proliferation. Graphic Abstract:

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Metadata

Authors
Jiang, F., Hedaya, O. M., Khor, E., Wu, J., Auguste, M., & Yao, P.
Affiliations
  • University of Rochester Medicine (US)
  • University of Rochester (US)
Corresponding author
Yao, Peng
ORCID
Venue
Nucleic Acids Research
Publisher
openRxiv
Published
2022-12-17
Volume
51
Issue
11
Pages
5831-5846
ISSN
0305-1048 (ISSN-L)
DOI
10.1101/2022.12.16.520836
PMC
PMC10287950
OpenAlex
W4367598503
Cited by
29
References
1
Citations by year
2026: 6 · 2025: 7 · 2024: 11 · 2023: 5
FWCI
2.58
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • American Heart Association (R01 HL147954, R01 HL132899, 848985)
  • University of Rochester
  • National Institutes of Health (848985)
  • Medical Center, University of Rochester
  • National Heart, Lung, and Blood Institute (R01HL147954, R01HL132899, R01HL164584, R01HL169432)
  • National Institute of General Medical Sciences (T32GM068411)
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
RNA-binding proteins, mRNA translation, post-transcriptional regulation, cyclin D2, G1/S transition, cell cycle progression, cell proliferation, eIF3, eIF4G2, translation initiation, oncogenes
MeSH terms
Cell Cycle, Cell Division, Humans, Protein Binding, RNA, Messenger, RNA-Binding Proteins, Eukaryotic Initiation Factor-3, Cyclin D2, HEK293 Cells

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