7CGK

Crystal Structure of PUF-8 in Complex with PBE-RNA

Summary for 7CGK

• Entry DOI: 10.2210/pdb7cgk/pdb
• Descriptor: PUM-HD domain-containing protein, PBE-5A (5'-R(P*UP*GP*UP*AP*AP*AP*UP*A)-3'), CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: complex, rna binding protein, puf protein
• Biological source: Caenorhabditis elegans; More
• Total number of polymer chains: 2
• Total formula weight: 44476.09

Authors

Zheng, X.,Yunyu, S.,Shouhong, G. (deposition date: 2020-07-01, release date: 2021-07-07, Last modification date: 2023-11-29)

Primary citation

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

PubMed 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.

PubMed: 34478557
DOI: 10.1093/nar/gkab754

Experimental method

X-RAY DIFFRACTION (2.4 Å)