한빛사논문
- 조회1,876
Abstract
Ping Wang,1,2,3 Katelyn A. Doxtader,1,2,3 and Yunsun Nam1,2,3,*
1 Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2 Division of Basic Reproductive Biology Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3 Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
*Correspondence: Yunsun Nam
Summary
N6-methyladenosine (m6A) is a prevalent, reversible chemical modification of functional RNAs and is important for central events in biology. The core m6A writers are Mettl3 and Mettl14, which both contain methyltransferase domains. How Mettl3 and Mettl14 cooperate to catalyze methylation of adenosines has remained elusive. We present crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. We determine that the heterodimeric complex of methyltransferase domains, combined with CCCH motifs, constitutes the minimally required regions for creating m6A modifications in vitro. We also show that Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition. Our model provides a molecular explanation for why certain mutations of Mettl3 and Mettl14 lead to impaired function of the methyltransferase complex.
논문정보
- Research article
- 2016년 06월 (BRIC 등록일 2016-07-19)
- 국외 연구진
- 생명과학 > 생화학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
