TY - JOUR
T1 - Genome-Wide Analysis of Human Long Noncoding RNAs
T2 - A Provocative Review
AU - Ponting, Chris P
AU - Haerty, Wilfried
N1 - Funding Information:
This work was funded by the Medical Research Council (MC_UU_00007/15), Wellcome (106956/Z/15/Z), and the Biotechnology and Biological Sciences Research Council Core Strategic Program (BB/CSP1720/1 and BBS/E/T/000PR9818) and Institute Strategic Program (BB/P016855/1 and BBS/E/T/000PR9783)
Publisher Copyright:
Copyright 2022 by Annual Reviews.
PY - 2022/8/31
Y1 - 2022/8/31
N2 - Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. The majority of evidence, we argue, indicates that most lncRNA transcript models reflect transcriptional noise or provide minor regulatory roles, leaving relatively few human lncRNAs that contribute centrally to human development, physiology, or behavior. These important few tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, and so resist simple categorization. This genome-wide view should help investigators prioritize individual lncRNAs based on their likely contribution to human biology.
AB - Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. The majority of evidence, we argue, indicates that most lncRNA transcript models reflect transcriptional noise or provide minor regulatory roles, leaving relatively few human lncRNAs that contribute centrally to human development, physiology, or behavior. These important few tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, and so resist simple categorization. This genome-wide view should help investigators prioritize individual lncRNAs based on their likely contribution to human biology.
KW - RNA structure
KW - evolutionary constraint
KW - knockout phenotype
KW - molecular mechanism
KW - subcellular localization
KW - transcriptional noise
U2 - 10.1146/annurev-genom-112921-123710
DO - 10.1146/annurev-genom-112921-123710
M3 - Review article
C2 - 35395170
SN - 1527-8204
VL - 23
SP - 153
EP - 172
JO - Annual Review of Genomics and Human Genetics
JF - Annual Review of Genomics and Human Genetics
ER -