The TRIM-NHL RNA-binding protein Brain Tumor coordinately regulates expression of the glycolytic pathway and vacuolar ATPase complex.

Autor:	Connacher RP; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA., Roden RT; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA., Huang KL; Department of Biochemistry and Biophysics, University of Rochester Medical Center, 575 Elmwood Avenue, Rochester, NY 14642, USA., Korte AJ; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA., Yeruva S; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA., Dittbenner N; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA., DesMarais AJ; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA., Weidmann CA; Department of Biological Chemistry, Center for RNA Biomedicine, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA., Randall TA; Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Williams J; Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Hall TMT; Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA., Wagner EJ; Department of Biochemistry and Biophysics, University of Rochester Medical Center, 575 Elmwood Avenue, Rochester, NY 14642, USA., Goldstrohm AC; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 1214A 6-155 Jackson Hall, 321 Church Street S.E., Minneapolis, MN 55455, USA.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Nov 11; Vol. 52 (20), pp. 12669-12688.
DOI:	10.1093/nar/gkae810
Abstrakt:	The essential Drosophila RNA-binding protein Brain Tumor (Brat) represses specific genes to control embryogenesis and differentiation of stem cells. In the brain, Brat functions as a tumor suppressor that diminishes neural stem cell proliferation while promoting differentiation. Though important Brat-regulated target mRNAs have been identified in these contexts, the full impact of Brat on gene expression remains to be discovered. Here, we identify the network of Brat-regulated mRNAs by performing RNA sequencing (RNA-seq) following depletion of Brat from cultured cells. We identify 158 mRNAs, with high confidence, that are repressed by Brat. De novo motif analysis identified a functionally enriched RNA motif in the 3' untranslated regions (UTRs) of Brat-repressed mRNAs that matches the biochemically defined Brat binding site. Integrative data analysis revealed a high-confidence list of Brat-repressed and Brat-bound mRNAs containing 3'UTR Brat binding motifs. Our RNA-seq and reporter assays show that multiple 3'UTR motifs promote the strength of Brat repression, whereas motifs in the 5'UTR are not functional. Strikingly, we find that Brat regulates expression of glycolytic enzymes and the vacuolar ATPase complex, providing new insight into its role as a tumor suppressor and the coordination of metabolism and intracellular pH. (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu