Involvement of SUMO conjugation in small nuclear RNA biogenesis

BRAGADO, LAUREANO; MAGALNIK, MELINA; POZZI, BERTA; SREBROW, ANABELLA

Colonia de sacramento

Congreso; 1ER CONGRESO BINACIONAL DE LOS CLUBES DEL ARN DE ARGENTINA Y URUGUAY; 2022

Club del ARN del Uruguay y Club argentino del ARN

Small nuclear RNAs snRNAS are non coding RNA molecules, which associate with a large set of proteins to form small nuclear ribonucleoprotein particles known as “ While the function of snRNAs and the assembly of snRNPs are well characterized, the regulation of snRNA gene expression is still poorly understood Most snRNAs are transcribed by RNAPII, including the major spliceosomal components U 1 U 2 U 4 and U 5 Unlike pre mRNAs, snRNAs are intronless and non polyadenylated RNAPII transcribes snRNA genes in close proximity to Cajal bodies ( Taking into account the relevance of snRNAs for spliceosome composition and function and consequently for the splicing process, that the regulation of the expression of these non coding RNAs is still poorly understood, together with previous work from our laboratory that demonstrated the importance of SUMO conjugation (or " for spliceosome assembly and catalytic activity, we decided to explore a possible connection between the SUMO machinery and the biogenesis of snRNAs, in particular those transcribed by RNA polymerase II W e have identified a variety of proteins that are part of the regulatory complexes of the different stages of snRNA biogenesis as bonafide SUMO conjugation targets We focused on SNAPC 1 a specific snRNA transcription factor that belongs to the SNAPc complex W e have observed that mutating lysine residues 245 and 333 drastically reduced SUMO conjugation to this protein This obtained SUMOylation deficient mutant (SNAPC 1 K 245 333 R) is unable to activate the transcription of some snRNA genes, despite the fact it is still recruited to the corresponding promoters This could indicate that SUMOylation of SNAPC 1 is required for SNAPc complex assembly or for this complex to recruit general transcription factors by this complex Surprisingly, we have observed that in certain mammalian cell lines, the overexpression of this mutant leads to cell death This could be due to a differential sensitivity to alterations in snRNA levels