title: PGL germ granule assembly protein is a base-specific, single-stranded RNase.
abstract: Cellular RNA-protein (RNP) granules are ubiquitous and have fundamental roles in biology and RNA metabolism, but the molecular basis of their structure, assembly, and function is poorly understood. Using nematode "P-granules" as a paradigm, we focus on the PGL granule scaffold protein to gain molecular insights into RNP granule structure and assembly. We first identify a PGL dimerization domain (DD) and determine its crystal structure. PGL-1 DD has a novel 13 α-helix fold that creates a positively charged channel as a homodimer. We investigate its capacity to bind RNA and discover unexpectedly that PGL-1 DD is a guanosine-specific, single-stranded endonuclease. Discovery of the PGL homodimer, together with previous results, suggests a model in which the PGL DD dimer forms a fundamental building block for P-granule assembly. Discovery of the PGL RNase activity expands the role of RNP granule assembly proteins to include enzymatic activity in addition to their job as structural scaffolds.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706;
authors.forename: Scott T
authors.initials: ST
authors.lastname: Aoki
authors.affiliation: Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Kershner
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706;
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bingman
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706;
authors.forename: Marvin
authors.initials: M
authors.lastname: Wickens
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706 jekimble@wisc.edu.
authors.forename: Judith
authors.initials: J
authors.lastname: Kimble
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002107:Caenorhabditis / Q000378:metabolism; D018360:Crystallography, X-Ray; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D012260:Ribonucleases
keywords: P-granules; PGL-1; PGL-3; RNA endonuclease; germ-cell development