Regulatory RNPs: A novel class of ribonucleoproteins that contribute to ribosome heterogeneity

Abstract

23Summary Statement: Processed scaRNAs give rise to a novel regulatory RNP which regulates the modification 24 of ribosomal RNA. These findings provide insight into the mechanisms governing ribosome 25 heterogeneity. 26 27 28All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/128090 doi: bioRxiv preprint first posted online Apr. 18, 2017; 2 Abstract 29 Ribonucleoproteins (RNPs), which are comprised of non-coding RNA and associated proteins, are involved in 30 essential cellular processes such as translation and pre-mRNA splicing. One class of RNP is the small Cajal 31 body-specific RNP (scaRNP), which contributes to the biogenesis of small nuclear RNPs (snRNPs) that are 32 central components of the spliceosome. Interestingly, three scaRNAs are internally processed, generating 33 stable nucleolus-enriched RNAs of unknown function. Here we provide evidence that these RNAs become part 34 of novel RNPs we term regulatory RNPs (regRNPs). We postulate that regRNPs can impact rRNA 35 modifications via interactions with the guide RNA component of small nucleolar RNPs (snoRNPs). Most 36 modifications within rRNA (predominantly pseudouridylation and ribose 2'-O-methylation) are conducted by 37 snoRNPs, and we hypothesize that the activity of at least some of these snoRNPs is under the control of 38 regRNPs. Ribosome heterogeneity leading to specialized ribosomes is an exciting emerging concept. Because 39 modifications within rRNA can vary in different physiological or pathological situations, rRNA modifications are 40 thought to be the major source of ribosome heterogeneity. Our identification of regRNPs thus provides 41 important and timely insight into how ribosome heterogeneity may be accomplished. This work also provides 42 additional functional connections between the Cajal body and the nucleolus. (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/128090 doi: bioRxiv preprint first posted online Apr. 18, 2017; 3 Introduction 48Ribosomal RNA (rRNA) is extensively modified (Khan and Maden, 1978; Maden, 1972; Maden and Salim, 49 1974), and occurs at precise locations (Maden, 1986; Maden, 1988). Two common modifications, the majority 50 of which are conducted by small nucleolar ribonucleoproteins (snoRNPs), are pseudouridylation and ribose 2'-51 O-methylation. There are two kinds of snoRNPs: box H/ACA (responsible for pseudouridylation) and box C/D 52 (responsible for 2'-O-methylation) (Kiss, 2004). Box H/ACA or box C/D snoRNAs have an antisense region 53 which base pairs with target rRNA and thereby facilitates the modification of rRNA target sites (Kiss, 2004). 54Recent evidence has shown that methylation modifications in rRNA are heterogeneous (Krogh et al., 2016) 55 (Incarnato ...