RESUMO
Fragments derived from small RNAs such as small nucleolar RNAs are biologically relevant but remain poorly understood. To address this gap, we developed sRNAfrag, a modular and interoperable tool designed to standardize the quantification and analysis of small RNA fragmentation across various biotypes. The tool outputs a set of tables forming a relational database, allowing for an in-depth exploration of biologically complex events such as multi-mapping and RNA fragment stability across different cell types. In a benchmark test, sRNAfrag was able to identify established loci of mature microRNAs solely based on sequencing data. Furthermore, the 5' seed sequence could be rediscovered by utilizing a visualization approach primarily applied in multi-sequence-alignments. Utilizing the relational database outputs, we detected 1411 snoRNA fragment conservation events between two out of four eukaryotic species, providing an opportunity to explore motifs through evolutionary time and conserved fragmentation patterns. Additionally, the tool's interoperability with other bioinformatics tools like ViennaRNA amplifies its utility for customized analyses. We also introduce a novel loci-level variance-score which provides insights into the noise around peaks and demonstrates biological relevance by distinctly separating breast cancer and neuroblastoma cell lines after dimension reduction when applied to small nucleolar RNAs. Overall, sRNAfrag serves as a versatile foundation for advancing our understanding of small RNA fragments and offers a functional foundation to further small RNA research. Availability: https://github.com/kenminsoo/sRNAfrag.
Assuntos
MicroRNAs , MicroRNAs/genética , Análise de Sequência de RNA/métodos , RNA Nucleolar Pequeno/genética , Biologia Computacional/métodos , Alinhamento de SequênciaRESUMO
Small nucleolar RNAs (snoRNAs) constitute a class of intron-derived non-coding RNAs ranging from 60 to 300 nucleotides. Canonically localized in the nucleolus, snoRNAs play a pivotal role in RNA modifications and pre-ribosomal RNA processing. Based on the types of modifications they involve, such as methylation and pseudouridylation, they are classified into two main families-box C/D and H/ACA snoRNAs. Recent investigations have revealed the unconventional synthesis and biogenesis strategies of snoRNAs, indicating their more profound roles in pathogenesis than previously envisioned. This review consolidates recent discoveries surrounding snoRNAs and provides insights into their mechanistic roles in cancer. It explores the intricate interactions of snoRNAs within signaling pathways and speculates on potential therapeutic solutions emerging from snoRNA research. In addition, it presents recent findings on the long non-coding small nucleolar RNA host gene (lncSNHG), a subset of long non-coding RNAs (lncRNAs), which are the transcripts of parental SNHGs that generate snoRNA. The nucleolus, the functional epicenter of snoRNAs, is also discussed. Through a deconstruction of the pathways driving snoRNA-induced oncogenesis, this review aims to serve as a roadmap to guide future research in the nuanced field of snoRNA-cancer interactions and inspire potential snoRNA-related cancer therapies.
Assuntos
Neoplasias , RNA Nucleolar Pequeno , Humanos , RNA Nucleolar Pequeno/genética , Ribossomos/metabolismo , RNA Ribossômico/metabolismo , Nucléolo Celular/metabolismo , Neoplasias/metabolismoRESUMO
Fragments derived from small RNAs such as small nucleolar RNAs hold biological relevance. However, they remain poorly understood, calling for more comprehensive methods for analysis. We developed sRNAfrag, a standardized workflow and set of scripts to quantify and analyze sRNA fragmentation of any biotype. In a benchmark, it is able to detect loci of mature microRNAs fragmented from precursors and, utilizing multi-mapping events, the conserved 5' seed sequence of miRNAs which we believe may extraoplate to other small RNA fragments. The tool detected 1411 snoRNA fragment conservation events between 2/4 eukaryotic species, providing the opportunity to explore motifs and fragmentation patterns not only within species, but between. Availability: https://github.com/kenminsoo/sRNAfrag.