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Given the success of Volume I of this Research Topic, and how rapidly the subject area is evolving, we are pleased to announce the launch of Volume II: The Role of Modifications in Regulatory ...

Given the success of Volume I of this Research Topic, and how rapidly the subject area is evolving, we are pleased to announce the launch of Volume II: The Role of Modifications in Regulatory Small RNAs:

Small noncoding RNAs have been discovered in diverse species across all three domains of life. Both canonical (e.g., miRNAs, piRNAs, and siRNAs) and non-canonical (e.g., tsRNAs, rsRNA, and ysRNAs) small RNAs can regulate gene expression at both transcriptional and post-transcriptional levels. While the RNA sequences may interact with transcripts/proteins through base-pair formation or tertiary structure binding form, emerging research has revealed that various RNA modifications are embedded in small RNAs (especially for non-canonical small RNAs). These small RNA modifications provide a second layer of regulation mechanism through modulating RNA properties such as stability and binding affinity, which afford the possibility to facilitate or obstruct the biochemical process that is involved in physiological conditions, responded to in environmental stimulations, or associated with in pathological symptoms.

With the expanding usage of high-throughput sequencing, increasing numbers of small RNA species have been discovered. However, traditional small RNA sequencing method lacks the capacity to detect small RNAs that carry specific RNA modifications, which may be problematic in obtaining accurate sequencing results. It is necessary to revisit the small RNA profile of tissues/cells by performing the improved small RNA-seq methods which can overcome the obstruction generated by RNA modifications during cDNA library construction processes.

While extensive efforts have been made to gather RNA modification information for large RNAs (e.g., mRNAs, lncRNAs, and circRNAs), small RNA modification analysis in biology and disease is limited. High-throughput LC-MS/MS based and sequencing-based approaches (e.g., CLIP-seq and Nanopore-based direct RNA sequencing) are practical ways to identify and pinpoint modification loci on small RNAs. These experimental technologies, along with bioinformatics tools, may provide new insights into the function of both canonical and non-canonical small RNAs as well as the regulatory roles of diverse RNA modifications. The complexity of small RNA along with its modification may also provide superior biomarkers with better resolution for the diagnosis and prognosis of diseases.

In this Research Topic we would like to reveal the hidden world of small RNAs that were previously ignored. Potential topics include, but are not limited to, the following:

• Identify small RNA profile by improved RNA sequencing method

• Classification and quantification of modifications on small RNAs

• Bioinformatics approaches to predict or analyze modified small RNAs

• Effect of RNA modifications on regulating small RNA function

• Dynamics of small RNA expression related to environmental stress and pathological processes

• Regulatory small RNAs as novel biomarkers in disease

Article types in original research, brief research report, methods, protocols, review, mini review, opinion, as well as perspective are all welcome to participate in this topic.

Keywords: #CollectionSeries, small noncoding RNA, modification, environmental stress, high-throughput sequencing, mass spectrometry, precision medicine

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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