RNA BiologyPub Date : 2023-01-01Epub Date: 2023-11-27DOI: 10.1080/15476286.2023.2279845
Sonia Chothani, Lena Ho, Sebastian Schafer, Owen Rackham
{"title":"Discovering microproteins: making the most of ribosome profiling data.","authors":"Sonia Chothani, Lena Ho, Sebastian Schafer, Owen Rackham","doi":"10.1080/15476286.2023.2279845","DOIUrl":"10.1080/15476286.2023.2279845","url":null,"abstract":"<p><p>Building a reference set of protein-coding open reading frames (ORFs) has revolutionized biological process discovery and understanding. Traditionally, gene models have been confirmed using cDNA sequencing and encoded translated regions inferred using sequence-based detection of start and stop combinations longer than 100 amino-acids to prevent false positives. This has led to small ORFs (smORFs) and their encoded proteins left un-annotated. Ribo-seq allows deciphering translated regions from untranslated irrespective of the length. In this review, we describe the power of Ribo-seq data in detection of smORFs while discussing the major challenge posed by data-quality, -depth and -sparseness in identifying the start and end of smORF translation. In particular, we outline smORF cataloguing efforts in humans and the large differences that have arisen due to variation in data, methods and assumptions. Although current versions of smORF reference sets can already be used as a powerful tool for hypothesis generation, we recommend that future editions should consider these data limitations and adopt unified processing for the community to establish a canonical catalogue of translated smORFs.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138446075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic and static circulating cancer microRNA biomarkers - a validation study.","authors":"Masood Abu-Halima, Andreas Keller, Lea Simone Becker, Ulrike Fischer, Annika Engel, Nicole Ludwig, Fabian Kern, Trine B Rounge, Hilde Langseth, Eckart Meese, Verena Keller","doi":"10.1080/15476286.2022.2154470","DOIUrl":"10.1080/15476286.2022.2154470","url":null,"abstract":"<p><p>For cancers and other pathologies, early diagnosis remains the most promising path to survival. Profiling of longitudinal cohorts facilitates insights into trajectories of biomarkers. We measured microRNA expression in 240 serum samples from patients with colon, lung, and breast cancer and from cancer-free controls. Each patient provided at least two serum samples, one prior to diagnosis and one following diagnosis. The median time interval between the samples was 11.6 years. Using computational models, we evaluated the circulating profiles of 21 microRNAs. The analysis yielded two sets of biomarkers, static ones that show an absolute difference between certain cancer types and controls and dynamic ones where the level over time provided higher diagnostic information content. In the first group, miR-99a-5p stands out for all three cancer types. In the second group, miR-155-5p allows to predict lung cancers and colon cancers. Classification in samples from cancer and non-cancer patients using gradient boosted trees reached an average accuracy of 79.9%. The results suggest that individual change over time or an absolute value at one time point may predict a disease with high specificity and sensitivity.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9754110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2023-01-01DOI: 10.1080/15476286.2023.2223484
Yanli Wang, Huiyong Li, Xiaojian Liu, Lu Gao, Yunhe Fan, Kun Yan Zhu, Jianzhen Zhang
{"title":"Three alternative splicing variants of <i>Loquacious</i> play different roles in miRNA- and siRNA-mediated RNAi pathways in <i>Locusta migratoria</i>.","authors":"Yanli Wang, Huiyong Li, Xiaojian Liu, Lu Gao, Yunhe Fan, Kun Yan Zhu, Jianzhen Zhang","doi":"10.1080/15476286.2023.2223484","DOIUrl":"https://doi.org/10.1080/15476286.2023.2223484","url":null,"abstract":"<p><p>RNA interference (RNAi) is a specific post-transcriptional gene-silencing phenomenon, which plays an important role in the regulation of gene expression and the protection from transposable elements in eukaryotic organisms. In <i>Drosophila melanogaster</i>, RNAi can be induced by microRNA (miRNA), endogenous small interfering RNA (siRNA), or exogenous siRNA. However, the biogenesis of miRNA and siRNA in these RNAi pathways is aided by the double-stranded RNA binding proteins (dsRBPs) Loquacious (Loqs)-PB, Loqs-PD or R2D2. In this study, we identified three alternative splicing variants of <i>Loqs</i>, namely <i>Loqs-PA</i>, -<i>PB</i>, and -<i>PC</i> in the orthopteran <i>Locusta migratoria</i>. We performed <i>in vitro</i> and <i>in vivo</i> experiments to study the roles of the three Loqs variants in the miRNA- and siRNA-mediated RNAi pathways. Our results show that Loqs-PB assists the binding of pre-miRNA to Dicer-1 to lead to the cleavage of pre-miRNA to yield matured miRNA in the miRNA-mediated RNAi pathway. In contrast, different Loqs proteins participate in different siRNA-mediated RNAi pathways. In exogenous siRNA-mediated RNAi pathway, binding of Loqs-PA or LmLoqs-PB to exogenous dsRNA facilitates the cleavage of dsRNA by Dicer-2, whereas in endogenous siRNA-mediated RNAi pathway, binding of Loqs-PB or Loqs-PC to endogenous dsRNA facilitates the cleavage of dsRNA by Dicer-2. Our findings provide new insights into the functional importance of different Loqs proteins derived from alternative splicing variants of <i>Loqs</i> in achieving high RNAi efficiency in different RNAi pathways in insects.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9687555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2023-01-01DOI: 10.1080/15476286.2023.2222250
Angelos Heldin, Matko Cancer, Mireia Palomar-Siles, Susanne Öhlin, Meiqiongzi Zhang, Alexander Sun-Zhang, Anna Mariani, Jianping Liu, Vladimir J N Bykov, Klas G Wiman
{"title":"Novel compounds that synergize with aminoglycoside G418 or eRF3 degraders for translational readthrough of nonsense mutant <i>TP53</i> and <i>PTEN</i>.","authors":"Angelos Heldin, Matko Cancer, Mireia Palomar-Siles, Susanne Öhlin, Meiqiongzi Zhang, Alexander Sun-Zhang, Anna Mariani, Jianping Liu, Vladimir J N Bykov, Klas G Wiman","doi":"10.1080/15476286.2023.2222250","DOIUrl":"https://doi.org/10.1080/15476286.2023.2222250","url":null,"abstract":"<p><p>The <i>TP53</i> and <i>PTEN</i> tumour suppressor genes are inactivated by nonsense mutations in a significant fraction of human tumours. <i>TP53</i> nonsense mutatant tumours account for approximately one million new cancer cases per year worldwide. We have screened chemical libraries with the aim of identifying compounds that induce translational readthrough and expression of full-length p53 protein in cells with nonsense mutation in this gene. Here we describe two novel compounds with readthrough activity, either alone or in combination with other known readthrough-promoting substances. Both compounds induced levels of full-length p53 in cells carrying R213X nonsense mutant <i>TP53</i>. Compound C47 showed synergy with the aminoglycoside antibiotic and known readthrough inducer G418, whereas compound C61 synergized with eukaryotic release factor 3 (eRF3) degraders CC-885 and CC-90009. C47 alone showed potent induction of full-length PTEN protein in cells with different <i>PTEN</i> nonsense mutations. These results may facilitate further development of novel targeted cancer therapy by pharmacological induction of translational readthrough.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10283442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9709443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2023-01-01DOI: 10.1080/15476286.2023.2192553
Jessica Nowacki, Mateo Malenica, Stefan Schmeing, Damian Schiller, Benjamin Buchmuller, Gulshan Amrahova, Peter 't Hart
{"title":"A translational repression reporter assay for the analysis of RNA-binding protein consensus sites.","authors":"Jessica Nowacki, Mateo Malenica, Stefan Schmeing, Damian Schiller, Benjamin Buchmuller, Gulshan Amrahova, Peter 't Hart","doi":"10.1080/15476286.2023.2192553","DOIUrl":"https://doi.org/10.1080/15476286.2023.2192553","url":null,"abstract":"<p><p>RNA-binding proteins are essential regulators of RNA processing and function. Translational repression assays can be used to study how they interact with specific RNA sequences by insertion of such a consensus sequence into the 5' untranslated region of a reporter mRNA and measuring reporter protein translation. The straightforward set-up of these translational repression assays avoids the need for the isolation of the protein or the RNA providing speed, robustness and a low-cost method. Here, we report the optimization of the assay to function with linear RNA sequences instead of the previously reported hairpin type sequences to allow the study of a wider variety of RNA-binding proteins. Multiplication of a consensus sequence strongly improves the signal allowing analysis by both fluorescence intensity measurements and flow cytometry.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/71/KRNB_20_2192553.PMC10038052.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9223154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Why are G-quadruplexes good at preventing protein aggregation?","authors":"Theodore J Litberg, Rajesh Kumar Reddy Sannapureddi, Zijue Huang, Ahyun Son, Bharathwaj Sathyamoorthy, Scott Horowitz","doi":"10.1080/15476286.2023.2228572","DOIUrl":"https://doi.org/10.1080/15476286.2023.2228572","url":null,"abstract":"<p><p>Maintaining a healthy protein folding environment is essential for cellular function. Recently, we found that nucleic acids, G-quadruplexes in particular, are potent chaperones for preventing protein aggregation. With the aid of structure-function and NMR analyses of two G-quadruplex forming sequences, PARP-I and LTR-III, we uncovered several contributing factors that affect G-quadruplexes in preventing protein aggregation. Notably, three factors emerged as vital in determining holdase activity of G-quadruplexes: their structural topology, G-quadruplex accessibility and dynamics, and oligomerization state. These factors together appear to largely dictate whether a G-quadruplex is able to prevent partially misfolded proteins from aggregating. Understanding the physical traits that govern the ability of G-quadruplexes to modulate protein aggregation will help elucidate their possible roles in neurodegenerative disease.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/64/KRNB_20_2228572.PMC10373610.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RNA origami: design, simulation and application.","authors":"Erik Poppleton, Niklas Urbanek, Taniya Chakraborty, Alessandra Griffo, Luca Monari, Kerstin Göpfrich","doi":"10.1080/15476286.2023.2237719","DOIUrl":"10.1080/15476286.2023.2237719","url":null,"abstract":"<p><p>Design strategies for DNA and RNA nanostructures have developed along parallel lines for the past 30 years, from small structural motifs derived from biology to large 'origami' structures with thousands to tens of thousands of bases. With the recent publication of numerous RNA origami structures and improved design methods-even permitting co-transcriptional folding of kilobase-sized structures - the RNA nanotechnolgy field is at an inflection point. Here, we review the key achievements which inspired and enabled RNA origami design and draw comparisons with the development and applications of DNA origami structures. We further present the available computational tools for the design and the simulation, which will be key to the growth of the RNA origami community. Finally, we portray the transition from RNA origami structure to function. Several functional RNA origami structures exist already, their expression in cells has been demonstrated and first applications in cell biology have already been realized. Overall, we foresee that the fast-paced RNA origami field will provide new molecular hardware for biophysics, synthetic biology and biomedicine, complementing the DNA origami toolbox.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9892884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2023-01-01Epub Date: 2023-09-24DOI: 10.1080/15476286.2023.2258028
Dana Segal, Samy Coulombe, Jasper Sim, Josée Dostie
{"title":"A conserved <i>HOTAIRM1-HOXA1</i> regulatory axis contributes early to neuronal differentiation.","authors":"Dana Segal, Samy Coulombe, Jasper Sim, Josée Dostie","doi":"10.1080/15476286.2023.2258028","DOIUrl":"10.1080/15476286.2023.2258028","url":null,"abstract":"<p><p>HOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream <i>HOXA</i> genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3' <i>HOXA</i> gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 participates in proper progression through the early stages of neuronal differentiation. We found that it can associate with the HOXA1 transcription factor and contributes to its downstream transcriptional program. Particularly, HOTAIRM1 affects the <i>NANOG</i>/<i>POU5F1</i>/<i>SOX2</i> core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved <i>HOTAIRM1-HOXA1</i> regulatory axis modulating the transition from a pluripotent to a differentiated neuronal state.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41179834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2023-01-01Epub Date: 2023-10-26DOI: 10.1080/15476286.2023.2272468
Zhanwei Wang, Hao Deng, Yao Jin, Meng Luo, Jia Huang, Jing Wang, Kun Zhang, Li Wang, Jiaojiao Zhou
{"title":"Circular RNAs: biology and clinical significance of breast cancer.","authors":"Zhanwei Wang, Hao Deng, Yao Jin, Meng Luo, Jia Huang, Jing Wang, Kun Zhang, Li Wang, Jiaojiao Zhou","doi":"10.1080/15476286.2023.2272468","DOIUrl":"10.1080/15476286.2023.2272468","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are novel noncoding RNAs with covalently closed-loop structures that can regulate eukaryotic gene expression. Due to their stable structure, circRNAs are widely distributed in the cytoplasm and have important biological functions, including as microRNA sponges, RNA-binding protein conjugates, transcription regulators, and translation templates. Breast cancer is among the most common malignant cancers diagnosed in women worldwide. Despite the development of comprehensive treatments, breast cancer still has high mortality rates. Recent studies have unmasked critical roles for circRNAs in breast cancer as regulators of tumour initiation, progression, and metastasis. Further, research has revealed that some circRNAs have the potential for use as diagnostic and prognostic biomarkers in clinical practice. Herein, we review the biogenesis and biological functions of circRNAs, as well as their roles in different breast cancer subtypes. Moreover, we provide a comprehensive summary of the clinical significance of circRNAs in breast cancer. CircRNAs are believed to be a hot focus in basic and clinical research of breast cancer, and innovative future research directions of circRNAs could be used as biomarkers, therapeutic targets, or novel drugs.<b>Abbreviations:</b> CeRNA: Competitive endogenous RNA; ciRNA: Circular intronic RNA; circRNA: Circular RNA; EIciRNA: Exon-intron circRNA; EMT: Epithelial-mesenchymal transition; IRES: Internal ribosome entry site; lncRNA: Long non-coding RNA; miRNA: MicroRNA; MRE: MiRNA response element; ncRNA: Non-coding RNA; RBP: RNA-binding protein; RNA-seq: RNA sequencing; RT-PCR: Reverse transcription-polymerase chain reaction.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2023-01-01Epub Date: 2023-10-26DOI: 10.1080/15476286.2023.2272118
Wei Wang, Lei Sun, Meng-Ting Huang, Yun Quan, Tao Jiang, Zhichao Miao, Qiong Zhang
{"title":"Regulatory circular RNAs in viral diseases: applications in diagnosis and therapy.","authors":"Wei Wang, Lei Sun, Meng-Ting Huang, Yun Quan, Tao Jiang, Zhichao Miao, Qiong Zhang","doi":"10.1080/15476286.2023.2272118","DOIUrl":"10.1080/15476286.2023.2272118","url":null,"abstract":"<p><p>Circular RNA (circRNA) forms closed loops via back-splicing in precursor mRNA, resisting exonuclease degradation. In higher eukaryotes, protein-coding genes create circRNAs through exon back-splicing. Unlike mRNAs, circRNAs possess unique production and structural traits, bestowing distinct cellular functions and biomedical potential. In this review, we explore the pivotal roles of viral circRNAs and associated RNA in various biological processes. Analysing the interactions between viral circRNA and host cellular machinery yields fresh insights into antiviral immunity, catalysing the development of potential therapeutics. Furthermore, circRNAs serve as enduring biomarkers in viral diseases due to their stable translation within specific tissues. Additionally, a deeper understanding of translational circRNA could expedite the establishment of circRNA-based expression platforms, meeting the rising demand for broad-spectrum viral vaccines. We also highlight the applications of circular RNA in biomarker studies as well as circRNA-based therapeutics. Prospectively, we expect a technological revolution in combating viral infections using circRNA.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50162729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}