Participacion de la conjugacion SUMO en la biogenesis de los snRNAs

BRAGADO, LAUREANO; POZZI, BERTA; SREBROW, ANABELLA

Parana

Congreso; 54th Annual Meeting Agentine Society for Biochemistry and Molecular Biology LIV Reunion Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2018

In addition to protein-coding genes, RNA polymerase II (Pol II) transcribes numerous genes that correspond to non-coding RNAs, including those of small nuclear RNAs (snRNAs). snRNAs are not only a fundamental component of the spliceosome but also some of them are necessary for the transcriptional activity of Pol II, as well as for maintaining cellular homeostasis.Although the functions of snRNAs are well understood, the regulation of their biogenesis is still not fully characterized. snRNA genes share common features with protein-coding genes, including the relative positioning of elements that control transcription and RNA processing. However, there are important differences in the set of proteins required for the proper expression and metabolism of these two gene types. SUMOylation is a reversible post-translational modificationconsisting in the conjugation of SUMO (small ubiquitin-related modifier) to different target proteins. It mainly regulates intra- and intermolecular interactions and consequently the function of a great variety of cellular proteins. We are currently studying the involvement of SUMO conjugation in snRNA biogenesis. So far, we have observed that modifying the levels of global SUMOylation in cultured mammalian cells alters the levels of nascent/immature snRNAs measured by RT-qPCR. Furthermore, we have identified that several regulatory factors involved in transcription, elongation and 3´-end processing of the snRNAs are modified by SUMO and we have determined the target lysine residues in some of them. We are currently exploring the functional consequences of abrogating this modification within these regulatory factors.