The Non-Coding Regulatory RNA Revolution in Archaea

Abstract

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3′ untranslated region (UTR), 5′ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved and how sRNAs integrate with complex regulatory networks.

Regulatory Noncoding Small RNAs Are Diverse and Abundant in an Extremophilic Microbial Community

“…This novel finding is representative of published work in model organisms, where a wide range of sRNAs has been found so far in prokaryotes, from less than a dozen to more than a thousand per genome (see Fig. S7 in the supplemental material) (1,5).…”

“…The roles of regulatory sRNAs have been extensively studied in Bacteria and, to a lesser extent, in archaeal model systems (1,5), but to date, only four studies have reported the discovery of sRNAs in microbial communities. In one study, Shi et al (6) used metatranscriptomic data to identify unique microbial intergenic sRNAs in the ocean's water column.…”

“…The functional roles of microbial sRNAs have been extensively studied in a few model organisms, and very little is known about the dynamics of sRNA synthesis in natural environments and the roles of these short transcripts at the community level (1,5). To our knowledge, only a few studies have reported the discovery of sRNAs in natural microbial communities (6)(7)(8)(9), and there is no publicly available bioinformatic tool for sRNA discovery in single-species isolates and in the metagenomic context (1). This paucity of knowledge suggests that an abundance of sRNAs remain to be discovered with potentially essential roles in stress response (10), interspecies communication, and/or cross-species RNA interference (11)(12)(13).…”

Regulatory non-coding small RNAs are diverse and abundant in an extremophilic microbial community

“…However, they do not overlap their target genes or bind their targets mRNAs with 429 perfect complementary, which make finding targets for these sRNAs very challenging 430 without genetic tools (Gelsinger and DiRuggiero 2018b). 431…”

Screening and verification of microRNA promoter methylation sites in hepatocellular carcinoma

“…An RNA that cannot encode a protein is known as a noncoding RNA (ncRNA) 6 . With the development of high‐throughput sequencing technology, the biological functions of the ncRNAs have been discovered gradually, 7,8 and dysfunction of ncRNAs can lead to the occurrence of many kinds of neoplasms, including HCC 9,10 . Some microRNAs are critical regulators in the development of HCC and are involved in the processes of proliferation, differentiation, metastasis, infiltration, apoptosis, and metabolism 11 …”