Wilson Briana, Esmaeili Fatemeh, Parsons Matthew, Salah Wafa, Su Zhangli, Dutta Anindya
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22901, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
iScience. 2024 Feb 20;27(3):109300. doi: 10.1016/j.isci.2024.109300. eCollection 2024 Mar 15.
microRNAs (miRNAs) are small regulatory RNAs that repress target mRNA transcripts through base pairing. Although the mechanisms of miRNA production and function are clearly established, new insights into miRNA regulation or miRNA-mediated gene silencing are still emerging. In order to facilitate the discovery of miRNA regulators or effectors, we have developed sRNA-Effector, a machine learning algorithm trained on enhanced crosslinking and immunoprecipitation sequencing and RNA sequencing data following knockdown of specific genes. sRNA-Effector can accurately identify known miRNA biogenesis and effector proteins and identifies 9 putative regulators of miRNA function, including serine/threonine kinase STK33, splicing factor SFPQ, and proto-oncogene BMI1. We validated the role of STK33, SFPQ, and BMI1 in miRNA regulation, showing that sRNA-Effector is useful for identifying new players in small RNA biology. sRNA-Effector will be a web tool available for all researchers to identify potential miRNA regulators in any cell line of interest.
微小RNA（miRNA）是一类小的调节性RNA，通过碱基配对抑制靶mRNA转录本。尽管miRNA产生和功能的机制已明确确立，但对miRNA调控或miRNA介导的基因沉默仍不断有新的见解涌现。为了促进miRNA调节因子或效应器的发现，我们开发了sRNA-Effector，这是一种机器学习算法，基于特定基因敲低后的增强交联和免疫沉淀测序以及RNA测序数据进行训练。sRNA-Effector能够准确识别已知的miRNA生物合成和效应蛋白，并鉴定出9种推测的miRNA功能调节因子，包括丝氨酸/苏氨酸激酶STK33、剪接因子SFPQ和原癌基因BMI1。我们验证了STK33、SFPQ和BMI1在miRNA调控中的作用，表明sRNA-Effector有助于识别小RNA生物学中的新参与者。sRNA-Effector将成为一个网络工具，供所有研究人员在任何感兴趣的细胞系中识别潜在的miRNA调节因子。
