title: Genome-wide analysis of Musashi-2 targets reveals novel functions in governing epithelial cell migration.
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.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Bennett
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Kent
authors.initials: K
authors.lastname: Riemondy
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Chapnick
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bunker
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Illumina Inc., 5602 Research Park Blvd. Suite 200, Madison, WI 53719, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Kuersten
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA yir@colorado.edu.
authors.forename: Rui
authors.initials: R
authors.lastname: Yi
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; C499059:Msi2h protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins