Genome-wide Analysis of Musashi-2 Targets Reveals Novel Functions in Governing Epithelial Cell Migration

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 Apr 2

PMID 27034466

Citations 36

Authors

Christopher G Bennett

Kent Riemondy

Douglas A Chapnick

Eric Bunker

Xuedong Liu

Scott Kuersten

Rui Yi

Affiliations

Soon will be listed here.

Abstract

The Musashi-2 (Msi2) RNA-binding protein maintains stem cell self-renewal and promotes oncogenesis by enhancing cell proliferation in hematopoietic and gastrointestinal tissues. However, it is unclear how Msi2 recognizes and regulates mRNA targets in vivo and whether Msi2 primarily controls cell growth in all cell types. Here we identified Msi2 targets with HITS-CLIP and revealed that Msi2 primarily recognizes mRNA 3'UTRs at sites enriched in multiple copies of UAG motifs in epithelial progenitor cells. RNA-seq and ribosome profiling demonstrated that Msi2 promotes targeted mRNA decay without affecting translation efficiency. Unexpectedly, the most prominent Msi2 targets identified are key regulators that govern cell motility with a high enrichment in focal adhesion and extracellular matrix-receptor interaction, in addition to regulators of cell growth and survival. Loss of Msi2 stimulates epithelial cell migration, increases the number of focal adhesions and also compromises cell growth. These findings provide new insights into the molecular mechanisms of Msi2's recognition and repression of targets and uncover a key function of Msi2 in restricting epithelial cell migration.

Citing Articles

Musashi-2 (MSI2) regulation of DNA damage response in lung cancer.

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Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA.

Singh S, Gaur A, Sharma R, Kumari R, Prakash S, Kumari S Basic Res Cardiol. 2023; 118(1):46.

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Acquired miR-142 deficit in leukemic stem cells suffices to drive chronic myeloid leukemia into blast crisis.

Zhang B, Zhao D, Chen F, Frankhouser D, Wang H, Pathak K Nat Commun. 2023; 14(1):5325.

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Musashi Exerts Control of Gonadotrope Target mRNA Translation During the Mouse Estrous Cycle.

Silva Moreira A, Lim J, Urbaniak A, Banik J, Bronson K, Lagasse A Endocrinology. 2023; 164(9).

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Regulation of VEGFR2 and AKT Signaling by Musashi-2 in Lung Cancer.

Bychkov I, Topchu I, Makhov P, Kudinov A, Patel J, Boumber Y Cancers (Basel). 2023; 15(9).

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