Antagonism between splicing and microprocessor complex dictates the serum-induced processing of lnc- MIRHG for efficient cell cycle reentry.

Autor:	Sun Q; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Hao Q; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Lin YC; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Song YJ; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Bangru S; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Arif W; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Tripathi V; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Zhang Y; School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA., Cho JH; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA., Freier SM; Ionis Pharmaceuticals Inc., Carlsbad, California 92008, USA., Jenkins LM; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA., Ma J; School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA., Yoon JH; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA., Kalsotra A; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Lal A; Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA., Prasanth SG; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA., Prasanth KV; Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.; Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Jazyk:	angličtina
Zdroj:	RNA (New York, N.Y.) [RNA] 2020 Nov; Vol. 26 (11), pp. 1603-1620. Date of Electronic Publication: 2020 Jul 16.
DOI:	10.1261/rna.075309.120
Abstrakt:	Cellular quiescence and cell cycle reentry regulate vital biological processes such as cellular development and tissue homeostasis and are controlled by precise regulation of gene expression. The roles of long noncoding RNAs (lncRNAs) during these processes remain to be elucidated. By performing genome-wide transcriptome analyses, we identify differential expression of several hundreds of lncRNAs, including a significant number of the less-characterized class of microRNA-host-gene ( MIRHG ) lncRNAs or lnc- MIRHGs , during cellular quiescence and cell cycle reentry in human diploid fibroblasts. We observe that MIR222HG lncRNA displays serum-stimulated RNA processing due to enhanced splicing of the host nascent pri- MIR222HG transcript. The pre-mRNA splicing factor SRSF1 negatively regulates the microprocessor-catalyzed cleavage of pri-miR-222, thereby increasing the cellular pool of the mature MIR222HG Association of SRSF1 to pri- MIR222HG , including to a mini-exon, which partially overlaps with the primary miR-222 precursor, promotes serum-stimulated splicing over microRNA processing of MIR222HG Further, we observe that the increased levels of spliced MIR222HG in serum-stimulated cells promote the cell cycle reentry post quiescence in a microRNA-independent manner. MIR222HG interacts with DNM3OS , another lncRNA whose expression is elevated upon serum-stimulation, and promotes cell cycle reentry. The double-stranded RNA binding protein ILF3/2 complex facilitates MIR222HG : DNM3OS RNP complex assembly, thereby promoting DNM3OS RNA stability. Our study identifies a novel mechanism whereby competition between the splicing and microprocessor machinery modulates the serum-induced RNA processing of MIR222HG , which dictates cell cycle reentry. (© 2020 Sun et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
Databáze:	MEDLINE
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