한빛사논문
- 조회1,703
Brice Laffleur1,5, Junghyun Lim1,2,5, Wanwei Zhang1,5, Yiyun Chen 3, Evangelos Pefanis1,4, Jonathan Bizarro1, Carolina R. Batista1, Lijing Wu1, Aris N. Economides4, Jiguang Wang3 and Uttiya Basu 1,*
1Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. 2Department of Pharmacy, School of Pharmacy, Jeonbuk National University, Jeonju, South Korea. 3Division of Life Science, Department of Chemical and Biological Engineering, Center for Systems Biology and Human Health, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China. 4Regeneron Pharmaceuticals, Tarrytown, NY, USA. 5These authors contributed equally: Brice Laffleur, Junghyun Lim, Wanwei Zhang.
*Corresponding author
Abstract
Noncoding RNAs are exquisitely titrated by the cellular RNA surveillance machinery for regulating diverse biological processes. The RNA exosome, the predominant 3′ RNA exoribonuclease in mammalian cells, is composed of nine core and two catalytic subunits. Here, we developed a mouse model with a conditional allele to study the RNA exosome catalytic subunit DIS3. In DIS3-deficient B cells, integrity of the immunoglobulin heavy chain (Igh) locus in its topologically associating domain is affected, with accumulation of DNA-associated RNAs flanking CTCF-binding elements, decreased CTCF binding to CTCF-binding elements and disorganized cohesin localization. DIS3-deficient B cells also accumulate activation-induced cytidine deaminase–mediated asymmetric nicks, altering somatic hypermutation patterns and increasing microhomology-mediated end-joining DNA repair. Altered mutation patterns and Igh architectural defects in DIS3-deficient B cells lead to decreased class-switch recombination but increased chromosomal translocations. Our observations of DIS3-mediated architectural regulation at the Igh locus are reflected genome wide, thus providing evidence that noncoding RNA processing is an important mechanism for controlling genome organization.
논문정보
- Research article
- 2021년 02월 (BRIC 등록일 2021-02-05)
- 국내+국외 연구진
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