Sjögren syndrome antigen B (SSB)/La promotes global microRNA expression by binding microRNA precursors through stem-loop recognition

Chunyang Liang, Ke Xiong, Keith E. Szulwach, Yi Zhang, Zhaohui Wang, Junmin Peng, Mingui Fu, Peng Jin, Hiroshi I. Suzuki, Qinghua Liu

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

MicroRNAs (miRNA) control numerous physiological and pathological processes. Typically, the primary miRNA (primiRNA) transcripts are processed by nuclear Drosha complex into ∼70-nucleotide stem-loop precursor miRNAs (premiRNA), which are further cleaved by cytoplasmic Dicer complex into ∼21-nucleotide mature miRNAs. However, it is unclear how nascent pre-miRNAs are protected from ribonucleases, such as MCPIP1, that degrade pre-miRNAs to abort miRNA production. Here, we identify Sjögren syndrome antigen B (SSB)/La as a pre-miRNA-binding protein that regulates miRNA processing in vitro. All three RNA-binding motifs (LAM, RRM1, and RRM2) of La/SSB are required for efficient pre-miRNA binding. Intriguingly, La/SSB recognizes the characteristic stem-loop structure of pre-miRNAs, of which the majority lack a 3′ UUU terminus. Moreover, La/SSB associates with endogenous pri-/pre-miRNAs and promotes miRNA biogenesis by stabilizing pre-miRNAs from nuclease (e.g. MCPIP1)-mediated decay in mammalian cells. Accordingly, we observed positive correlations between the expression status of La/SSB and Dicer in human cancer transcriptome and prognosis. These studies identify an important function of La/SSB as a global regulator of miRNA expression, and implicate stem-loop recognition as a major mechanism that mediates association between La/SSB and diverse RNA molecules.

Original languageEnglish (US)
Pages (from-to)723-736
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number1
DOIs
StatePublished - Jan 4 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Liang, C., Xiong, K., Szulwach, K. E., Zhang, Y., Wang, Z., Peng, J., Fu, M., Jin, P., Suzuki, H. I., & Liu, Q. (2013). Sjögren syndrome antigen B (SSB)/La promotes global microRNA expression by binding microRNA precursors through stem-loop recognition. Journal of Biological Chemistry, 288(1), 723-736. https://doi.org/10.1074/jbc.M112.401323