bims-smotar 2023-02-26 papers

Issue of 2023–02–26
six papers selected by
Rabia T. Khan, Serna Bio

Biology (Basel). 2023 Jan 21. pii: 172. [Epub ahead of print]12(2):

Viroids: Non-Coding Circular RNAs Able to Autonomously Replicate and Infect Higher Plants.

Viroids are a unique type of infectious agent, exclusively composed of a relatively small (246-430 nt), highly base-paired, circular, non-coding RNA. Despite the small size and non-coding nature, the more-than-thirty currently known viroid species infectious of higher plants are able to autonomously replicate and move systemically through the host, thereby inducing disease in some plants. After recalling viroid discovery back in the late 60s and early 70s of last century and discussing current hypotheses about their evolutionary origin, this article reviews our current knowledge about these peculiar infectious agents. We describe the highly base-paired viroid molecules that fold in rod-like or branched structures and viroid taxonomic classification in two families, Pospiviroidae and Avsunviroidae, likely gathering nuclear and chloroplastic viroids, respectively. We review current knowledge about viroid replication through RNA-to-RNA rolling-circle mechanisms in which host factors, notably RNA transporters, RNA polymerases, RNases, and RNA ligases, are involved. Systemic movement through the infected plant, plant-to-plant transmission and host range are also discussed. Finally, we focus on the mechanisms of viroid pathogenesis, in which RNA silencing has acquired remarkable importance, and also for the initiation of potential biotechnological applications of viroid molecules.

Keywords: RNA silencing; circular RNA; hammerhead ribozyme; host plant; infectious agent; non-coding RNA; rolling-circle replication

DOI: https://doi.org/10.3390/biology12020172

Sci Rep. 2023 Feb 17. 13(1): 2861

RNA independent fragment partition method based on deep learning for RNA secondary structure prediction.

Qi Zhao, Qian Mao, Zheng Zhao, Wenxuan Yuan, Qiang He, Qixuan Sun, Yudong Yao, Xiaoya Fan.

The non-coding RNA secondary structure largely determines its function. Hence, accuracy in structure acquisition is of great importance. Currently, this acquisition primarily relies on various computational methods. The prediction of the structures of long RNA sequences with high precision and reasonable computational cost remains challenging. Here, we propose a deep learning model, RNA-par, which could partition an RNA sequence into several independent fragments (i-fragments) based on its exterior loops. Each i-fragment secondary structure predicted individually could be further assembled to acquire the complete RNA secondary structure. In the examination of our independent test set, the average length of the predicted i-fragments was 453 nt, which was considerably shorter than that of complete RNA sequences (848 nt). The accuracy of the assembled structures was higher than that of the structures predicted directly using the state-of-the-art RNA secondary structure prediction methods. This proposed model could serve as a preprocessing step for RNA secondary structure prediction for enhancing the predictive performance (especially for long RNA sequences) and reducing the computational cost. In the future, predicting the secondary structure of long-sequence RNA with high accuracy can be enabled by developing a framework combining RNA-par with various existing RNA secondary structure prediction algorithms. Our models, test codes and test data are provided at https://github.com/mianfei71/RNAPar .

DOI: https://doi.org/10.1038/s41598-023-30124-x

Noncoding RNA. 2023 Jan 21. pii: 10. [Epub ahead of print]9(1):

Computational Methods to Study DNA:DNA:RNA Triplex Formation by lncRNAs.

Timothy Warwick, Ralf P Brandes, Matthias S Leisegang.

Long non-coding RNAs (lncRNAs) impact cell function via numerous mechanisms. In the nucleus, interactions between lncRNAs and DNA and the consequent formation of non-canonical nucleic acid structures seems to be particularly relevant. Along with interactions between single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA), such as R-loops, ssRNA can also interact with double-stranded DNA (dsDNA) to form DNA:DNA:RNA triplexes. A major challenge in the study of DNA:DNA:RNA triplexes is the identification of the precise RNA component interacting with specific regions of the dsDNA. As this is a crucial step towards understanding lncRNA function, there exist several computational methods designed to predict these sequences. This review summarises the recent progress in the prediction of triplex formation and highlights important DNA:DNA:RNA triplexes. In particular, different prediction tools (Triplexator, LongTarget, TRIPLEXES, Triplex Domain Finder, TriplexFFP, TriplexAligner and Fasim-LongTarget) will be discussed and their use exemplified by selected lncRNAs, whose DNA:DNA:RNA triplex forming potential was validated experimentally. Collectively, these tools revealed that DNA:DNA:RNA triplexes are likely to be numerous and make important contributions to gene expression regulation.

Keywords: DNA:DNA:RNA triplex formation; DNA–RNA triplex; interaction of DNA and RNA; long non-coding RNA; triplex

DOI: https://doi.org/10.3390/ncrna9010010

Front Endocrinol (Lausanne). 2023 ;14 1149857

Editorial: Non-coding RNA in diabetes and cardiovascular diseases.

Mirjana T Macvanin, Sonja Zafirovic, Milan Obradovic, Esma R Isenovic.

Keywords: Non-coding RNA as a therapeutic target; cardiovascular diseases; circular RNAs; diabetes; long non-coding RNAs; microRNAs; non-coding RNA

DOI: https://doi.org/10.3389/fendo.2023.1149857

mBio. 2023 Feb 21. e0345022

Stress Response in Entamoeba histolytica Is Associated with Robust Processing of tRNA to tRNA Halves.

Manu Sharma, Hanbang Zhang, Gretchen Ehrenkaufer, Upinder Singh.

tRNA-derived fragments have been reported in many different organisms and have diverse cellular roles, such as regulating gene expression, inhibiting protein translation, silencing transposable elements, and modulating cell proliferation. In particular, tRNA halves, a class of tRNA fragments produced by the cleavage of tRNAs in the anti-codon loop, have been widely reported to accumulate under stress and regulate translation in cells. Here, we report the presence of tRNA-derived fragments in Entamoeba, with tRNA halves being the most abundant. We further established that tRNA halves accumulate in the parasites upon different stress stimuli such as oxidative stress, heat shock, and serum starvation. We also observed differential expression of tRNA halves during developmental changes of trophozoite-to-cyst conversion, with various tRNA halves accumulating during early encystation. In contrast to other systems, the stress response does not appear to be mediated by a few specific tRNA halves, as multiple tRNAs appear to be processed during the various stresses. Furthermore, we identified some tRNA-derived fragments associated with Entamoeba Argonaute proteins, EhAgo2-2 and EhAgo2-3, which have a preference for different tRNA-derived fragment species. Finally, we show that tRNA halves are packaged inside extracellular vesicles secreted by amoebas. The ubiquitous presence of tRNA-derived fragments, their association with the Argonaute proteins, and the accumulation of tRNA halves during multiple different stresses, including encystation, suggest a nuanced level of gene expression regulation mediated by different tRNA-derived fragments in Entamoeba. IMPORTANCE In the present study, we report for the first time the presence of tRNA-derived fragments in Entamoeba. tRNA-derived fragments were identified by bioinformatics analyses of small-RNA sequencing data sets from the parasites and also confirmed experimentally. We found that tRNA halves accumulated in parasites exposed to environmental stress or during the developmental process of encystation. We also found that shorter tRNA-derived fragments are bound to Entamoeba Argonaute proteins, indicating that they may have a potential role in the Argonaute-mediated RNA-interference pathway, which mediates robust gene silencing in Entamoeba. We noticed that in response to heat shock, the protein translation levels were elevated in the parasites. This effect was reversed in the presence of an analog of leucine, which also reduced the levels of the tRNA halves in the stressed cells. Our results suggest that tRNA-derived fragments in Entamoeba have a possible role in regulating gene expression during environmental stress.

Keywords: Entamoeba; encystation; tRNA halves; tRNA-derived fragments

DOI: https://doi.org/10.1128/mbio.03450-22

Nat Struct Mol Biol. 2023 Feb 23.

A shape-shifting nuclease unravels structured RNA.

Katarina Meze, Armend Axhemi, Dennis R Thomas, Ahmet Doymaz, Leemor Joshua-Tor.

RNA turnover pathways ensure appropriate gene expression levels by eliminating unwanted transcripts. Dis3-like 2 (Dis3L2) is a 3'-5' exoribonuclease that plays a critical role in human development. Dis3L2 independently degrades structured substrates, including coding and noncoding 3' uridylated RNAs. While the basis for Dis3L2's substrate recognition has been well characterized, the mechanism of structured RNA degradation by this family of enzymes is unknown. We characterized the discrete steps of the degradation cycle by determining cryogenic electron microscopy structures representing snapshots along the RNA turnover pathway and measuring kinetic parameters for RNA processing. We discovered a dramatic conformational change that is triggered by double-stranded RNA (dsRNA), repositioning two cold shock domains by 70 Å. This movement exposes a trihelix linker region, which acts as a wedge to separate the two RNA strands. Furthermore, we show that the trihelix linker is critical for dsRNA, but not single-stranded RNA, degradation. These findings reveal the conformational plasticity of Dis3L2 and detail a mechanism of structured RNA degradation.

DOI: https://doi.org/10.1038/s41594-023-00923-x