6FDL

Crystal structure of the NYN domain of human MARF1

Summary for 6FDL

• Entry DOI: 10.2210/pdb6fdl/pdb
• Descriptor: Meiosis regulator and mRNA stability factor 1 (2 entities in total)
• Functional Keywords: mrna turnover, decapping, deadenylation-independent decapping, nyn domain, ribonuclease, rna, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 36466.66

Authors

Jinek, M.,Brandmann, T. (deposition date: 2017-12-26, release date: 2018-11-07, Last modification date: 2024-10-16)

Primary citation

Nishimura, T.,Fakim, H.,Brandmann, T.,Youn, J.Y.,Gingras, A.C.,Jinek, M.,Fabian, M.R.
Human MARF1 is an endoribonuclease that interacts with the DCP1:2 decapping complex and degrades target mRNAs.
Nucleic Acids Res., 46:12008-12021, 2018

PubMed Abstract: Meiosis arrest female 1 (MARF1) is a cytoplasmic RNA binding protein that is essential for meiotic progression of mouse oocytes, in part by limiting retrotransposon expression. MARF1 is also expressed in somatic cells and tissues; however, its mechanism of action has yet to be investigated. Human MARF1 contains a NYN-like domain, two RRMs and eight LOTUS domains. Here we provide evidence that MARF1 post-transcriptionally silences targeted mRNAs. MARF1 physically interacts with the DCP1:DCP2 mRNA decapping complex but not with deadenylation machineries. Importantly, we provide a 1.7 Å resolution crystal structure of the human MARF1 NYN domain, which we demonstrate is a bona fide endoribonuclease, the activity of which is essential for the repression of MARF1-targeted mRNAs. Thus, MARF1 post-transcriptionally represses gene expression by serving as both an endoribonuclease and as a platform that recruits the DCP1:DCP2 decapping complex to targeted mRNAs.

PubMed: 30364987
DOI: 10.1093/nar/gky1011

Experimental method

X-RAY DIFFRACTION (1.75 Å)