TY - JOUR
T1 - Challenges and strategies in ascribing functions to long noncoding RNAs
AU - Zhao, Yang
AU - Teng, Hongqi
AU - Yao, Fan
AU - Yap, Shannon
AU - Sun, Yutong
AU - Ma, Li
N1 - Funding Information:
Y.S. is supported by MD Anderson’s Cancer Center Support Grant from the US National Cancer Institute (NCI P30CA016672). L.M. is supported by NCI grants R01CA166051 and R01CA181029 and a Cancer Prevention & Research Institute of Texas grant RP190029.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6
Y1 - 2020/6
N2 - Long noncoding RNAs (lncRNAs) are involved in many physiological and pathological processes, such as development, aging, immunity, and cancer. Mechanistically, lncRNAs exert their functions through interaction with proteins, genomic DNA, and other RNA, leading to transcriptional and post-transcriptional regulation of gene expression, either in cis or in trans; it is often difficult to distinguish between these two regulatory mechanisms. A variety of approaches, including RNA interference, antisense oligonucleotides, CRISPR-based methods, and genetically engineered mouse models, have yielded abundant information about lncRNA functions and underlying mechanisms, albeit with many discrepancies. In this review, we elaborate on the challenges in ascribing functions to lncRNAs based on the features of lncRNAs, including the genomic location, copy number, domain structure, subcellular localization, stability, evolution, and expression pattern. We also describe a framework for the investigation of lncRNA functions and mechanisms of action. Rigorous characterization of cancer-implicated lncRNAs is critical for the identification of bona fide anticancer targets.
AB - Long noncoding RNAs (lncRNAs) are involved in many physiological and pathological processes, such as development, aging, immunity, and cancer. Mechanistically, lncRNAs exert their functions through interaction with proteins, genomic DNA, and other RNA, leading to transcriptional and post-transcriptional regulation of gene expression, either in cis or in trans; it is often difficult to distinguish between these two regulatory mechanisms. A variety of approaches, including RNA interference, antisense oligonucleotides, CRISPR-based methods, and genetically engineered mouse models, have yielded abundant information about lncRNA functions and underlying mechanisms, albeit with many discrepancies. In this review, we elaborate on the challenges in ascribing functions to lncRNAs based on the features of lncRNAs, including the genomic location, copy number, domain structure, subcellular localization, stability, evolution, and expression pattern. We also describe a framework for the investigation of lncRNA functions and mechanisms of action. Rigorous characterization of cancer-implicated lncRNAs is critical for the identification of bona fide anticancer targets.
KW - CRISPR
KW - In cis
KW - In trans
KW - LncRNA
UR - http://www.scopus.com/inward/record.url?scp=85086104784&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086104784&partnerID=8YFLogxK
U2 - 10.3390/cancers12061458
DO - 10.3390/cancers12061458
M3 - Review article
C2 - 32503290
AN - SCOPUS:85086104784
SN - 2072-6694
VL - 12
SP - 1
EP - 21
JO - Cancers
JF - Cancers
IS - 6
M1 - 1458
ER -