The G-patch protein NF-?B-repressing factor mediates the recruitment of the exonuclease XRN2 and activation of the RNA helicase DHX15 in human ribosome biogenesis.

ABSTRACT: In eukaryotes, the synthesis of ribosomal subunits, which involves the maturation of the ribosomal (r)RNAs and assembly of ribosomal proteins, requires the co-ordinated action of a plethora of ribosome biogenesis factors. Many of these cofactors remain to be characterized in human cells. Here, we demonstrate that the human G-patch protein NF-?B-repressing factor (NKRF) forms a pre-ribosomal subcomplex with the DEAH-box RNA helicase DHX15 and the 5?-3? exonuclease XRN2. Using UV crosslinking and analysis of cDNA (CRAC), we reveal that NKRF binds to the transcribed spacer regions of the pre-rRNA transcript. Consistent with this, we find that depletion of NKRF, XRN2 or DHX15 impairs an early pre-rRNA cleavage step (A'). The catalytic activity of DHX15, which we demonstrate is stimulated by NKRF functioning as a cofactor, is required for efficient A' cleavage, suggesting that a structural remodelling event may facilitate processing at this site. In addition, we show that depletion of NKRF or XRN2 also leads to the accumulation of excised pre-rRNA spacer fragments and that NKRF is essential for recruitment of the exonuclease to nucleolar pre-ribosomal complexes. Our findings therefore reveal a novel pre-ribosomal subcomplex that plays distinct roles in the processing of pre-rRNAs and the turnover of excised spacer fragments.

SUBMITTER: Memet I 

PROVIDER: S-EPMC5435916 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature