SnoRNA guide activities: real and ambiguous

Abstract

In eukaryotes, rRNAs and spliceosomal snRNAs are heavily modified posttranscriptionally. Pseudouridylation and 2’-O-methylation are the most abundant types of RNA modifications. They are mediated by modification guide RNAs, also known as small nucleolar (sno)RNAs and small Cajal body-specific (sca)RNAs. We used yeast and vertebrate cells to test guide activities predicted for a number of snoRNAs, based on their regions of complementarity with rRNAs. We showed that human SNORA24 is a genuine guide RNA for 18S-ψ609, despite some non-canonical base-pairing with its target. At the same time, we found quite a few snoRNAs that have the ability to base-pair with rRNAs and can induce predicted modifications in artificial substrate RNAs, but do not modify the same target sequence within endogenous rRNA molecules. Furthermore, certain fragments of rRNAs can be modified by the endogenous yeast modification machinery when inserted into an artificial backbone RNA, even though the same sequences are not modified in endogenous yeast rRNAs. In Xenopus cells a guide RNA generated from scaRNA, but not from snoRNA, could induce an additional pseudouridylation of U2 snRNA at position 60; both guide RNAs were equally active on a U2 snRNA-specific substrate in yeast cells. Thus, posttranscriptional modification of functionally important RNAs, such as rRNAs and snRNAs, is highly regulated and more complex than simply strong base-pairing between a guide RNA and substrate RNA. We discuss possible regulatory roles for these unexpected modifications.

Changes in the Small Noncoding RNAome During M1 and M2 Macrophage Polarization

“…They often serve as guides for posttranscriptional modification of rRNA. According to their sequence, structure and function, they can be divided into two categories: Box C/D snoRNA and Box H/ACA snoRNA ( 27 ). All snoRNAs are paired with specific proteins to form small nucleolar ribonucleoprotein complexes.…”

Epigenetic modification regulates tumor progression and metastasis through EMT (Review)

“…This type of snoRNA carries out methyluracilylation modification to the base of RNA. Its characteristic is to form a double stem and add a loop area in the middle, among which boxH in the middle loop area ( 224 ). Long non-coding RNAs (lncRNAs) are longer than 200 bp and are transcribed from independent promoters by RNA Pol II ( 225 ).…”

Small Nucleolar RNAs and Their Comprehensive Biological Functions in Hepatocellular Carcinoma

“…A low level of SNORA24 played a critical role in tumor initiation and progression and in the ability to evade the tumor-suppressive defense mechanism conferred by OIS. SNORA24 was mainly responsible for pseudouridine modifications of two sites in the 18S rRNA of the small 40S subunit: uridine 609 and uridine 863 [ 67 , 68 ]. SNORA24 influenced multiple aspects of mRNA translation.…”