Guan Lingyu, Vaidhyanathan Sathyanarayanan, Grigoriev Andrey
Department of Biology, Center for Computational and Integrative Biology, Rutgers University, Camden, New Jersey 08102, USA.
Department of Biology, Center for Computational and Integrative Biology, Rutgers University, Camden, New Jersey 08102, USA
RNA. 2025 Mar 18;31(4):486-496. doi: 10.1261/rna.080285.124.
rRNA-derived fragments (rRFs) are a class of emerging posttranscriptional regulators of gene expression likely binding to the transcripts of target genes. However, the lack of knowledge about such targets hinders our understanding of rRF functions or binding mechanisms. The paucity of resources supporting the identification of the targets of rRFs creates a bottleneck in the fast-developing field. We have previously analyzed chimeric reads in cross-linked Argonaute1-RNA complexes to help infer the guide-target pairs and binding mechanisms of multiple rRFs based on experimental data in human HEK293 cells. To efficiently disseminate these results to the research community, we designed a web-based database rRFtargetDB that preserves most of the experimental results after the removal of noise and has a user-friendly interface with flexible query options and filters allowing users to obtain comprehensive information on rRFs (or targets) of interest. rRFtargetDB is populated by ∼163,000 experimentally determined unique rRF-mRNA pairs (∼60,000 supported by ≥2 reads). Almost 30,000 rRF isoforms produced >385,000 (>156,000 with ≥2 reads) chimeras with all types of RNA targets (mRNAs and noncoding RNAs). Further analyses suggested hypothetical modes of interactions, supported by secondary structures of potential guide-target hybrids and binding motifs, essential for understanding the targeting mechanisms of rRFs. All these results (ranging from the weakest to the strongest experimental support) are presented in rRFtargetDB, whose goal is to provide a resource for building users' hypotheses on the potential roles of rRFs for experimental validation. Further, we illustrate the value/application of the database in several examples.rRFtargetDB is freely accessible at https://grigoriev-lab.camden.rutgers.edu/tardb.
核糖体RNA衍生片段(rRFs)是一类新出现的基因表达转录后调节因子,可能与靶基因的转录本结合。然而,由于对这类靶标的了解不足,阻碍了我们对rRF功能或结合机制的理解。支持鉴定rRF靶标的资源匮乏,在这个快速发展的领域形成了一个瓶颈。我们之前分析了交联的AGO1-RNA复合物中的嵌合 reads,以基于人类HEK293细胞中的实验数据,帮助推断多个rRF的引导-靶标对和结合机制。为了将这些结果有效地传播给研究群体,我们设计了一个基于网络的数据库rRFtargetDB,该数据库在去除噪声后保留了大部分实验结果,并具有用户友好的界面,带有灵活的查询选项和过滤器,允许用户获取有关感兴趣的rRF(或靶标)的全面信息。rRFtargetDB包含约163,000个通过实验确定的独特rRF-mRNA对(约60,000个由≥2条reads支持)。近30,000个rRF异构体与所有类型的RNA靶标(mRNA和非编码RNA)产生了超过385,000个(≥2条reads的超过156,000个)嵌合体。进一步的分析提出了假设的相互作用模式,这些模式得到了潜在引导-靶标杂交体的二级结构和结合基序的支持,这对于理解rRF的靶向机制至关重要。所有这些结果(从最弱到最强的实验支持)都呈现在rRFtargetDB中,其目标是提供一个资源,用于构建用户关于rRF潜在作用的假设,以便进行实验验证。此外,我们在几个例子中说明了该数据库的价值/应用。rRFtargetDB可在https://grigoriev-lab.camden.rutgers.edu/tardb免费访问。