Degenerate consensus sequences in the 3′-untranslated regions of cellular mRNAs as specific motifs potentially involved in the YB-1-mediated packaging of these mRNAs

Alexander V. Gopanenko, Alexey A. Malygin, Olga A. Kossinova, Alexey E. Tupikin, Marsel R. Kabilov, Galina G. Karpova

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The multifunctional protein YB-1 has previously been shown to be the only protein of the cytoplasmic extract of HEK293 cells, which is able to specifically interact with imperfect RNA hairpins containing motifs that are often found in exosomal (e) RNAs. In addition, it has been revealed that similar hairpins formed by degenerate consensus sequences corresponding to three eRNA-specific motifs are responsible for the cooperative binding of YB-1 to RNA in vitro. Here, using the photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation method applied to HEK293 cells producing FLAG-labeled YB-1, we identified mRNAs cross-linked to YB-1 in vivo and then carried out a search for the aforementioned sequences in the regions of the YB-1 cross-linking sites. It turned out that many of the mRNAs found cross-linked to YB-1 encode proteins associated with various regulatory processes, including responses to stress. More than half of all cross-linked mRNAs contained degenerate consensus sequences, which were preferably located in 3′-untranslated regions (UTRs), where most of the YB-1 cross-linking sites appeared, although not close to these sequences. Furthermore, YB-1 was mainly cross-linked to those mRNAs with degenerate consensus sequences, which could be classified as packaged because their translation levels were low compared to cellular levels. This suggests that the cooperative binding of YB-1 to mRNAs through the above sequences probably triggers the well-known multimerization of YB-l, leading to the packaging of these mRNAs. Thus, our findings indicate a previously unknown link between the degenerate consensus sequences present in the 3′-UTRs of many cytoplasmic mRNAs and YB-1-mediated translational silencing.

Original languageEnglish
Pages (from-to)152-162
Number of pages11
JournalBiochimie
Volume170
Early online date13 Jan 2020
DOIs
Publication statusPublished - Mar 2020

Keywords

  • mRNA consensus sequences
  • mRNA packaging
  • Photoactivatable-ribonucleoside enhancing cross-linking and immunoprecipitation
  • Regulation of gene expression
  • RNA-protein interactions
  • YB-1
  • CELLS
  • COMPLEXES
  • MECHANISMS
  • BINDING PROTEIN
  • TRANSLATION
  • YB-1 BINDS
  • GENOME-WIDE ANALYSIS

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