The essential role of architectural noncoding RNA Neat1 in cold-induced beige adipocyte differentiation in mice
- Hikaru Toya1,
- Yuko Okamatsu-Ogura2,
- Saori Yokoi1,
- Misuzu Kurihara1,
- Mari Mito3,
- Shintaro Iwasaki3,
- Tetsuro Hirose4 and
- Shinichi Nakagawa1
- 1RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
- 2Laboratory of Biochemistry, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan
- 3RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama 351-0198, Japan
- 4RNA Biofunction Laboratory, Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan
- Corresponding author: nakagawas{at}pharm.hokudai.ac.jp
Abstract
Neat1 is an architectural RNA that provides the structural basis for nuclear bodies known as paraspeckles. Although the assembly processes by which Neat1 organizes paraspeckle components are well-documented, the physiological functions of Neat1 are not yet fully understood. This is partly because Neat1 knockout (KO) mice, lacking paraspeckles, do not exhibit overt phenotypes under normal laboratory conditions. During our search for conditions that elicit clear phenotypes in Neat1 KO 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 of Neat1, 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 for Neat1 and paraspeckles in modulating chromosomal organization and gene expression, potentially crucial processes for the differentiation of beige adipocytes.
Keywords
- Neat1
- paraspeckles
- cold exposure
- beige adipocytes
- knockout mice
- nondomain biopolymer
- intrinsically disordered regions
- Received January 30, 2024.
- Accepted April 8, 2024.
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