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Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA...
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Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA Fragments in Human Health and Disease

A special issue of Non-Coding RNA (ISSN 2311-553X). This special issue belongs to the section "Small Non-Coding RNA".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 12302

Special Issue Editors

Dr. Eric Londin

E-Mail Website
Guest Editor
Computational Medicine Center, Department of Pathology, Anatomy and Cellular Biology Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: next-generation sequencing; microRNAs; non-coding RNAs; transcriptome; bioinformatics
Special Issues, Collections and Topics in MDPI journals
Dr. Cameron Bracken

E-Mail Website
Guest Editor
Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, Australia
Interests: microRNAs; noncoding RNA; gene expression; cell signalling
Special Issues, Collections and Topics in MDPI journals
Dr. Yohei Kirino

E-Mail Website1 Website2
Guest Editor
Department of Biochemistry and Molecular Biology, and Computational Medicine Center at Thomas Jefferson University, Philadelphia, PA, USA
Interests: short non-coding RNA, cyclic phosphate-containing RNA, tRNA-derived RNA, tRNA half
Dr. Isidore Rigoutsos

E-Mail Website
Guest Editor
Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
Interests: microRNAs (miRNAs) and miRNA isoforms (isomiRs); tRNA-derived fragments (tRFs); rRNA-derived fragments (rRFs); post-transcriptional regulation; pyknons; repetitive elements; genomic architecture

Special Issue Information

Dear Colleagues,

Small RNAs are known to play essential roles in numerous cellular contexts. Among the various RNA classes, the microRNAs (miRNAs) and their isoforms (isomiRs), the tRNA-derived fragments (tRFs), and the rRNA-derived fragments (rRFs) have been attracting much attention during the last decade. Quickly accumulating evidence suggests that all three classes are useful for designing powerful diagnostics and prognostics and as novel therapeutic targets. 

IsomiRs, tRFs, and rRFs arise non-randomly from miRNA precursors, tRNAs, and rRNAs, respectively. Which of these small RNAs are produced from a precursor molecule and at what abundance level depends on personal attributes (e.g., biological sex, ancestry, age) and context (e.g., cell type, disease type/subtype). Moreover, while some isomiRs, tRFs, and rRFs regulate mRNA and protein levels through RNA interference, it is unclear how most of them function.

This Special Issue of “Noncoding RNA” focuses on isomiRs, tRFs, and rRFs and the many open questions surrounding them. Manuscripts reporting original research, short communications, and methods will be of particular interest. Focused reviews will also be considered. 

The following is a non-exhaustive list of themes of interest:

  • Novel insights into the biogenesis of isomiRs, tRFs, and rRFs.
  • Novel insights into how isomiRs, tRFs, and rRFs regulate gene expression.
  • Previously unreported patterns of expression in health and disease.
  • Reports of novel disease biomarkers or prognostics based on these small RNAs.
  • Functionalization of specific small RNAs.
  • Evolutionary aspects of isomiRs, tRNA fragments, and rRNA fragments.
  • Experimental methods for the accurate detection and quantification of these small RNAs.

Dr. Eric Londin
Dr. Cameron Bracken
Dr. Yohei Kirino
Dr. Isidore Rigoutsos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microRNA
  • miRNA
  • miRNA isoform
  • isomiR
  • tRNA
  • tRNA-derived fragment
  • tRF
  • rRNA
  • rRNA-derived fragment
  • rRF
  • biomarker
  • diagnostic
  • prognostic
  • therapeutic
  • small RNA

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Published Papers (4 papers)

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Research

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16 pages, 2610 KiB  
Article
sRNAflow: A Tool for the Analysis of Small RNA-Seq Data
by Pawel Zayakin
Non-Coding RNA 2024, 10(1), 6; https://doi.org/10.3390/ncrna10010006 - 17 Jan 2024
Viewed by 3809
Abstract
The analysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that hold potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from [...] Read more.
The analysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that hold potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods. Full article
(This article belongs to the Special Issue Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA Fragments in Human Health and Disease)
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18 pages, 761 KiB  
Article
The Typical tRNA Co-Expresses Multiple 5′ tRNA Halves Whose Sequences and Abundances Depend on Isodecoder and Isoacceptor and Change with Tissue Type, Cell Type, and Disease
by Robert Brian Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas J. Tsiouplis, Phillipe Loher and Isidore Rigoutsos
Non-Coding RNA 2023, 9(6), 69; https://doi.org/10.3390/ncrna9060069 - 6 Nov 2023
Cited by 2 | Viewed by 2933
Abstract
Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several [...] Read more.
Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several co-expressed 5’-tRNA halves (5′-tRHs) that differ in the location of their 3′ ends. These 5′-tRHs, even though distinct, have traditionally been treated as indistinguishable from one another due to their near-identical sequences and lengths. We focused on co-expressed 5′-tRHs that arise from the same tRNA and systematically examined their exact sequences and abundances across 10 different human tissues. To this end, we manually curated and analyzed several hundred human RNA-seq datasets from NCBI’s Sequence Run Archive (SRA). We grouped datasets from the same tissue into their own collection and examined each group separately. We found that a given tRNA produces different groups of co-expressed 5′-tRHs in different tissues, different cell lines, and different diseases. Importantly, the co-expressed 5′-tRHs differ in their sequences, absolute abundances, and relative abundances, even among tRNAs with near-identical sequences from the same isodecoder or isoacceptor group. The findings suggest that co-expressed 5′-tRHs that are produced from the same tRNA or closely related tRNAs have distinct, context-dependent roles. Moreover, our analyses show that cell lines modeling the same tissue type and disease may not be interchangeable when it comes to experimenting with tRFs. Full article
(This article belongs to the Special Issue Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA Fragments in Human Health and Disease)
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Review

Jump to: Research

17 pages, 2749 KiB  
Review
Functions of RNAi Pathways in Ribosomal RNA Regulation
by Aleksei S. Shatskikh, Elena A. Fefelova and Mikhail S. Klenov
Non-Coding RNA 2024, 10(2), 19; https://doi.org/10.3390/ncrna10020019 - 29 Mar 2024
Viewed by 2017
Abstract
Argonaute proteins, guided by small RNAs, play crucial roles in gene regulation and genome protection through RNA interference (RNAi)-related mechanisms. Ribosomal RNAs (rRNAs), encoded by repeated rDNA units, constitute the core of the ribosome being the most abundant cellular transcripts. rDNA clusters also [...] Read more.
Argonaute proteins, guided by small RNAs, play crucial roles in gene regulation and genome protection through RNA interference (RNAi)-related mechanisms. Ribosomal RNAs (rRNAs), encoded by repeated rDNA units, constitute the core of the ribosome being the most abundant cellular transcripts. rDNA clusters also serve as sources of small RNAs, which are loaded into Argonaute proteins and are able to regulate rDNA itself or affect other gene targets. In this review, we consider the impact of small RNA pathways, specifically siRNAs and piRNAs, on rRNA gene regulation. Data from diverse eukaryotic organisms suggest the potential involvement of small RNAs in various molecular processes related to the rDNA transcription and rRNA fate. Endogenous siRNAs are integral to the chromatin-based silencing of rDNA loci in plants and have been shown to repress rDNA transcription in animals. Small RNAs also play a role in maintaining the integrity of rDNA clusters and may function in the cellular response to rDNA damage. Studies on the impact of RNAi and small RNAs on rRNA provide vast opportunities for future exploration. Full article
(This article belongs to the Special Issue Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA Fragments in Human Health and Disease)
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20 pages, 1349 KiB  
Review
A Review of IsomiRs in Colorectal Cancer
by Molly A. Lausten and Bruce M. Boman
Non-Coding RNA 2023, 9(3), 34; https://doi.org/10.3390/ncrna9030034 - 7 Jun 2023
Cited by 3 | Viewed by 2539
Abstract
As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known [...] Read more.
As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on microRNA isoforms in CRC. The information on isomiRs presented herein shows that isomiRs hold great promise for translation into new diagnostics and therapeutics in clinical medicine. Full article
(This article belongs to the Special Issue Small RNAs – Big Roles: IsomiRs, tRNA Fragments, and rRNA Fragments in Human Health and Disease)
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