Physiological roles of long noncoding RNAs: insight from knockout mice

Abstract

Long noncoding RNAs (lncRNAs) are a pervasive and recently recognized class of genes. lncRNAs have been proposed to modulate gene expression and nuclear architecture, but their physiological functions are still largely unclear. Several recent efforts to inactivate lncRNA genes in mouse models have shed light on their functions. Different genetic strategies have yielded specific lessons about the roles of lncRNA transcription, the lncRNA transcript itself, and underlying sequence elements. Current results indicate important functions for lncRNAs in organ development, immunity, organismal viability, and in human diseases.

Keywords: gene targeting; genetic study; knockout; lncRNA; phenotype.

Figure 1. Genetic strategies to study lncRNA loci

(A) Complete deletion (i) or replacement (ii), (B) promoter deletion, or (C) premature termination can reveal different requirements of lncRNA transcription, RNA product, or underlying sequences in biological function. √ denotes the strategy tests the indicated mechanism; X denotes the strategy does not interrogate the indicated mechanism (“(X)”, under debate).

Figure 2. Highlights of lncRNA functions in vivo

LncRNA knockout (KO) results in multiple defects in mouse development and cancer progression. The diagram shows representative phenotypes and several knockout examples are listed below. cKO, conditional knockout.