C. Elegans integrator complexidentification and analysis of a role beyond snrna processing

Résumé

In this work we described the C. elegans Integrator complex and the involvement of its INTS-6 subunit in DNA damage response. The Integrator complex, which is comprised of at least fourteen subunits in human cells, is responsible for snRNA 3’-end processing. In addition, some of its subunits are involved in other steps of the RNAP II transcription cycle or other biological processes such as development or DNA repair. Here, we demonstrated that the C. elegans Integrator complex is comprised of, at least, eleven subunits (INTS-1, INTS-2, INTS-3, INTS-4, INTS-5, INTS-6, INTS-7, INTS-8, INTS-9, INTS-11 and INTS-13). RNAi knockdown of any subunit leads to 3’- end processing defects that result in the formation of chimeric RNAs composed of an snRNA and an mRNA, which we have called “sn-mRNAs”’. We also detected these chimeric “sn-mRNAs” upon gamma radiation. Finally, involvement of INTS-6 in DNA repair via the HR pathway was demonstrated and we suggested a link between INTS-6 in DSB DNA repair and the formation of chimeric “sn-mRNAs”.