The essential role of architectural noncoding RNANeat1in cold-induced beige adipocyte differentiation in mice

Abstract

Neat1is an architectural RNA that provides the structural basis for nuclear bodies known as paraspeckles. Although the assembly processes by whichNeat1organizes paraspeckle components are well-documented, the physiological functions ofNeat1are not yet fully understood. This is partly becauseNeat1knockout (KO) mice, lacking paraspeckles, do not exhibit overt phenotypes under normal laboratory conditions. During our search for conditions that elicit clear phenotypes inNeat1KO mice, we discovered that the differentiation of beige adipocytes—inducible thermogenic cells that emerge upon cold exposure—is severely impaired in these mutant mice.Neat1_2, the architectural isoform ofNeat1, is transiently upregulated during the early stages of beige adipocyte differentiation, coinciding with increased paraspeckle formation. Genes with altered expression during beige adipocyte differentiation typically cluster at specific chromosomal locations, some of which move closer to paraspeckles upon cold exposure. These observations suggest that paraspeckles might coordinate the regulation of these gene clusters by controlling the activity of certain transcriptional condensates that coregulate multiple genes. We propose that our findings highlight a potential role forNeat1and paraspeckles in modulating chromosomal organization and gene expression, potentially crucial processes for the differentiation of beige adipocytes.