Pol3Base: a resource for decoding the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs

Abstract

RNA polymerase III (Pol III) transcribes hundreds of non-coding RNA genes (ncRNAs), which involve in a variety of cellular processes. However, the expression, functions, regulatory networks and evolution of these Pol III-transcribed ncRNAs are still largely unknown. In this study, we developed a novel resource, Pol3Base (http://rna.sysu.edu.cn/pol3base/), to decode the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs. The current release of Pol3Base includes thousands of regulatory relationships between ∼79 000 ncRNAs and transcription factors by mining 56 ChIP-seq datasets. By integrating CLIP-seq datasets, we deciphered the interactions of these ncRNAs with >240 RNA binding proteins. Moreover, Pol3Base contains ∼9700 RNA modifications located within thousands of Pol III-transcribed ncRNAs. Importantly, we characterized expression profiles of ncRNAs in >70 tissues and 28 different tumor types. In addition, by comparing these ncRNAs from human and mouse, we revealed about 4000 evolutionary conserved ncRNAs. We also identified ∼11 403 tRNA-derived small RNAs (tsRNAs) in 32 different tumor types. Finally, by analyzing somatic mutation data, we investigated the mutation map of these ncRNAs to help uncover their potential roles in diverse diseases. This resource will help expand our understanding of potential functions and regulatory networks of Pol III-transcribed ncRNAs.

The molecular language of RNA 5′ ends: guardians of RNA identity and immunity

“…In mammals, most of the ncRNAs transcribed by the RNA polymerase III bear a 5′-PPP end, suggesting that in certain settings these transcripts could be aberrantly recognized by some innate immune sensors as pathogenic. RNA polymerase III transcribed RNAs include, 5S rRNA, tRNAs, 7SL RNAs, U6 snRNA, RNase P and MRP RNAs, small nucleolar RNAs, 7SK RNA, Alu RNAs, vault RNAs (vRNAs), and Y RNAs ( Dieci et al 2007 ; Cai et al 2022 ). In addition to the host's genes, RNA polymerase III can also transcribe the genome of DNA viruses, thus generating 5′-PPP RNAs that can be recognized by RIG-I, thus amplifying the innate immune response ( Jarrous and Rouvinski 2021 ; Naesens et al 2023 ).…”

NAP-seq reveals multiple classes of structured noncoding RNAs with regulatory functions

“…More than 80% of the human genome can be transcribed into RNA 1 by three RNA polymerases: RNA polymerase I (Pol I) 2 – 4 , RNA polymerase II (Pol II) 5 , 6 and RNA polymerase III (Pol III) 4 , 7 , 8 . These transcribed RNAs are further processed into capped RNAs (capRNAs) 9 , 10 and noncapped RNAs (napRNAs).…”

Crosstalk between vault RNAs and innate immunity

“…In mammals, a significant number of noncoding RNAs (ncRNAs) transcribed by RNA polymerase III (RNA Pol III) bear 5ʹ-triphosphate (5ʹ-PPP) termini, suggesting that these RNAs can trigger viral nucleic acid sensors [ 37 ]. This group of RNA Pol III-transcribed ncRNAs includes transfer RNAs (tRNAs), 7SL RNAs, 7SK RNAs, 5S rRNA, U6 small nuclear RNAs (snRNAs), YRNAs, Alu RNAs, and vault (vt) RNAs [ 38 – 43 ]. Furthermore, these ncRNAs have been linked to pathological processes associated with systemic inflammation, which is often driven by the abnormal production of interferon type I (IFN-I) [ 44 – 47 ].…”