气候变化领域集成服务门户(CCPortal): miRNA-independent function of long noncoding pri-miRNA loci

CCPortal

DOI	10.1073/pnas.2017562118
	miRNA-independent function of long noncoding pri-miRNA loci
	He D.; Wu D.; Muller S.; Wang L.; Saha P.; Ahanger S.H.; Liu S.J.; Cui M.; Hong S.J.; Jain M.; Olson H.E.; Akeson M.; Costello J.F.; Diaz A.; Lim D.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1–independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Host gene; Lnc-pri-miRNA; LncRNA; MiRNA
语种	英语
scopus关键词	long untranslated RNA; microRNA; microRNA 29a; microRNA b1; unclassified drug; Article; cell proliferation; controlled study; gene cluster; gene deletion; gene function; gene interaction; gene knockdown; gene locus; glioblastoma cell line; human; human cell; MKLN1 gene; oncogene; priority journal; promoter region
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180079
作者单位	Department of Neurological Surgery, Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, United States; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, United States; Developmental and Stem Cell Biology Graduate Program, Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, United States; Medical Scientist Training Program, Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, United States; Department of Surgery, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, United States; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, United States; UCSC Genomics Institute, University of California, Santa Cruz, CA 95064, United States
推荐引用方式 GB/T 7714	He D.,Wu D.,Muller S.,et al. miRNA-independent function of long noncoding pri-miRNA loci[J],2021,118(13).
APA	He D..,Wu D..,Muller S..,Wang L..,Saha P..,...&Lim D.A..(2021).miRNA-independent function of long noncoding pri-miRNA loci.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	He D.,et al."miRNA-independent function of long noncoding pri-miRNA loci".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).