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Home  > Press Release  > The tRNA pseudouridine synthase TruB1 regulates the maturation of let-7 miRNA

The tRNA pseudouridine synthase TruB1 regulates the maturation of let-7 miRNA

Abstract

Let‐7 is an evolutionary conserved microRNA that mediates post‐transcriptional gene silencing to regulate a wide range of biological processes, including development, differentiation, and tumor suppression. Let‐7 biogenesis is tightly regulated by several RNA‐binding proteins, including Lin28A/B, which represses let‐7 maturation. To identify new regulators of let‐7, we devised a cell‐based functional screen of RNA‐binding proteins using a let‐7 sensor luciferase reporter and identified the tRNA pseudouridine synthase, TruB1. TruB1 enhanced maturation specifically of let‐7 family members. Rather than inducing pseudouridylation of the miRNAs, high‐throughput sequencing crosslinking immunoprecipitation (HITS‐CLIP) and biochemical analyses revealed direct binding between endogenous TruB1 and the stem‐loop structure of pri‐let‐7, which also binds Lin28A/B. TruB1 selectively enhanced the interaction between pri‐let‐7 and the microprocessor DGCR8, which mediates miRNA maturation. Finally, TruB1 suppressed cell proliferation, which was mediated in part by let‐7. Altogether, we reveal an unexpected function for TruB1 in promoting let‐7 maturation.

Journal Article

JOURNAL:
The EMBO Journal

TITLE:
The tRNA pseudouridine synthase TruB1 regulates the maturation of let-7 miRNA

DOI:
https://doi.org/10.15252/embj.2020104708

Correspondence to

Hiroshi ASAHARA, MD, Ph.D., Professor
Department of Systems BioMedicine,
Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University(TMDU)
E-mail:asahara.syst(at)tmd.ac.jp


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