Interaction between the human proteins SEPT3 and PM-Scl75/hRrp45: analysis of the connection between septin filaments and the exosome complex

Abstract

Our research group is part of the Center for Structural Molecular Biotechnology (CBME), which is part of the CEPID-FAPESP program. CBME laboratory members are developing an integrated project to determine the structure and function of the 14 human septins. Initial functional assays are focusing on the identification of septin-interacting partners using the yeast two-hybrid system. By using this system, we have identified septin 6 (SEPT6) and 11 (SEPT11) as septin 3 (SEPT3) interacting proteins. We have also isolated six additional proteins that interact with SEPt3 in this system, including the exosome subunit hRrp45, which corresponds also to the Pm-Scl75 autoantigen that is detected in sera from myositis, scleroderma and polymyositis-scleroderma overlap syndromes. The exosome is a complex of exoribonucleases found in the nucleus and cytoplasm that functions in pre-rRNA (pre-ribosomal RNA) and sno-RNAs (small nucleolar RNAs) maturation and in degradation of mRNAs and of the excised spacer sequences of the pre-rRNA. The interaction of SEPT3 with the exosome subunit hRrp45 is intriguing and indicates a possible functional interaction between septin filaments and the exosome. Consisting with this finding is a study showing that the exosome subunit Dis3 plays a role in cell division in the fission yeast Schizosaccharomyces pombe. It was shown that in S. pombe, the function of Dis3 (ortholog of the exosome subunit hRrp44) is required for proper formation of the kinetocore and for the interaction between the kinetocore and microtubules. However, there is little information in the literature about the impact of the exosome on cell division and no information on physical and physiological interactions between the exosome and septins. Therefore, we plan to characterize the interaction between SETP3 and hRrp45PM/Scl-75 in this work which is expected to generate novel information on the activity and regulation of the exosome complex and the human septins and on the possible implications of the septin-exosome interaction on cell division. (AU)