title: SCD6 induces ribonucleoprotein granule formation in trypanosomes in a translation-independent manner, regulated by its Lsm and RGG domains.
abstract: Ribonucleoprotein (RNP) granules are cytoplasmic, microscopically visible structures composed of RNA and protein with proposed functions in mRNA decay and storage. Trypanosomes have several types of RNP granules, but lack most of the granule core components identified in yeast and humans. The exception is SCD6/Rap55, which is essential for processing body (P-body) formation. In this study, we analyzed the role of trypanosome SCD6 in RNP granule formation. Upon overexpression, the majority of SCD6 aggregates to multiple granules enriched at the nuclear periphery that recruit both P-body and stress granule proteins, as well as mRNAs. Granule protein composition depends on granule distance to the nucleus. In contrast to findings in yeast and humans, granule formation does not correlate with translational repression and can also take place in the nucleus after nuclear targeting of SCD6. While the SCD6 Lsm domain alone is both necessary and sufficient for granule induction, the RGG motif determines granule type and number: the absence of an intact RGG motif results in the formation of fewer granules that resemble P-bodies. The differences in granule number remain after nuclear targeting, indicating translation-independent functions of the RGG domain. We propose that, in trypanosomes, a local increase in SCD6 concentration may be sufficient to induce granules by recruiting mRNA. Proteins that bind selectively to the RGG and/or Lsm domain of SCD6 could be responsible for regulating granule type and number.
authors.affiliation: Lehrstuhl für Zell- und Entwicklungsbiologie, Biozentrum, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
authors.forename: Timothy
authors.initials: T
authors.lastname: Krüger
authors.forename: Mario
authors.initials: M
authors.lastname: Hofweber
authors.forename: Susanne
authors.initials: S
authors.lastname: Kramer
mesh_terms: D000595:Amino Acid Sequence; D003594:Cytoplasmic Granules / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D003598:Cytoskeletal Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins