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Annual Review of Genomics and Human Genetics

Volume 23, 2022

Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review

Abstract

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.

Keyword(s): evolutionary constraint, knockout phenotype, molecular mechanism, RNA structure, subcellular localization, transcriptional noise
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/content/journals/10.1146/annurev-genom-112921-123710
2022-08-31
2024-05-17
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Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review
Annual Review of Genomics and Human Genetics 23, 153 (2022); https://doi.org/10.1146/annurev-genom-112921-123710
/content/journals/10.1146/annurev-genom-112921-123710
/content/journals/10.1146/annurev-genom-112921-123710
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