SNAP annotations: PDB entry 7cgh

PDB-id

7cgh; DSSR-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

X-ray (2.4 Å)

Summary

Crystal structure of puf-8 in complex with pbe-RNA

Reference

Xu Z, Zhao J, Hong M, Zeng C, Guang S, Shi Y (2021): "Structural recognition of the mRNA 3' UTR by PUF-8 restricts the lifespan of C. elegans." Nucleic Acids Res., 49, 10082-10097. doi: 10.1093/nar/gkab754.

Abstract

The molecular mechanisms of aging are unsolved fundamental biological questions. Caenorhabditis elegans is an ideal model organism for investigating aging. PUF-8, a PUF (Pumilio and FBF) protein in C. elegans, is crucial for germline development through binding with the 3' untranslated regions (3' UTR) in the target mRNAs. Recently, PUF-8 was reported to alter mitochondrial dynamics and mitophagy by regulating MFF-1, a mitochondrial fission factor, and subsequently regulated longevity. Here, we determined the crystal structure of the PUF domain of PUF-8 with an RNA substrate. Mutagenesis experiments were performed to alter PUF-8 recognition of its target mRNAs. Those mutations reduced the fertility and extended the lifespan of C. elegans. Deep sequencing of total mRNAs from wild-type and puf-8 mutant worms as well as in vivo RNA Crosslinking and Immunoprecipitation (CLIP) experiments identified six PUF-8 regulated genes, which contain at least one PUF-binding element (PBE) at the 3' UTR. One of the six genes, pqm-1, is crucial for lipid storage and aging process. Knockdown of pqm-1 could revert the lifespan extension of puf-8 mutant animals. We conclude that PUF-8 regulate the lifespan of C. elegans may not only via MFF but also via modulating pqm-1-related pathways.