Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA

Baronti, Lorenzo; Guzzetti, Ileana; Ebrahimi, Parisa; Sandoz, Sarah Friebe; Steiner, Emilie; Schlagnitweit, Judith; Fromm, Bastian; Silva, Luís; Fontana, Carolina; Chen, Alan; Petzold, Katja

doi:10.1038/s41586-020-2336-3

Cited by 53 publications

(75 citation statements)

References 57 publications

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“…Here, we demonstrate an application involving secondary structure determination of RNA "ESs" that form through reshuffling base pairs in and around noncanonical motifs. RNA ESs involving the local rearrangement of the secondary structure are of great interest 31,32 as they are linked to functional regulation 33,34 , enzymatic catalysis 34 , ligand binding [35][36][37] , and folding/unfolding 38,39 . These reshuffling motions usually fall into microsecond to millisecond time regime since only a few base pairings are changed during the exchange process.…”

Section: Resultsmentioning

confidence: 99%

Chemical shift prediction of RNA imino groups: application toward characterizing RNA excited states

et al. 2021

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NH groups in proteins or nucleic acids are the most challenging target for chemical shift prediction. Here we show that the RNA base pair triplet motif dictates imino chemical shifts in its central base pair. A lookup table is established that links each type of base pair triplet to experimental chemical shifts of the central base pair, and can be used to predict imino chemical shifts of RNAs to remarkable accuracy. Strikingly, the semiempirical method can well interpret the variations of chemical shifts for different base pair triplets, and is even applicable to non-canonical motifs. This finding opens an avenue for predicting chemical shifts of more complicated RNA motifs. Furthermore, we combine the imino chemical shift prediction with NMR relaxation dispersion experiments targeting both 15N and 1HN of the imino group, and verify a previously characterized excited state of P5abc subdomain including an earlier speculated non-native G•G mismatch.

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Section: Resultsmentioning

confidence: 99%

Chemical shift prediction of RNA imino groups: application toward characterizing RNA excited states

et al. 2021

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“…Such a hypothesis, if confirmed, could represent an important change in our understanding of the flow of biological information within the organisms. Likewise, the frontier of the universe of small RNAs is constantly expanding [ 134 ], with new microRNAs species being identified uninterruptedly, as well as their molecular idiosyncrasies [ 135 , 136 , 137 , 138 ]. Thus, diverse still hidden aspects of miRNA-prion interplay and cross-regulation may come to light in the upcoming years.…”

Section: Perspectivesmentioning

confidence: 99%

MicroRNAs in Prion Diseases—From Molecular Mechanisms to Insights in Translational Medicine

Contiliani

Ribeiro

Moraes

et al. 2021

Cells

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MicroRNAs (miRNAs) are small non-coding RNA molecules able to post-transcriptionally regulate gene expression via base-pairing with partially complementary sequences of target transcripts. Prion diseases comprise a singular group of neurodegenerative conditions caused by endogenous, misfolded pathogenic (prion) proteins, associated with molecular aggregates. In humans, classical prion diseases include Creutzfeldt–Jakob disease, fatal familial insomnia, Gerstmann–Sträussler–Scheinker syndrome, and kuru. The aim of this review is to present the connections between miRNAs and prions, exploring how the interaction of both molecular actors may help understand the susceptibility, onset, progression, and pathological findings typical of such disorders, as well as the interface with some prion-like disorders, such as Alzheimer’s. Additionally, due to the inter-regulation of prions and miRNAs in health and disease, potential biomarkers for non-invasive miRNA-based diagnostics, as well as possible miRNA-based therapies to restore the levels of deregulated miRNAs on prion diseases, are also discussed. Since a cure or effective treatment for prion disorders still pose challenges, miRNA-based therapies emerge as an interesting alternative strategy to tackle such defying medical conditions.

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“…MicroRNAs (miRNAs/miRs) form a large family of ncRNAs with a length of 19-22 nucleotides, and dysregulation of miRNAs is involved in cancer development and progression (8). Since the first miRNA (lin-4) was identified by Lee et al (9) in 1993, the role of miRNAs in tumors has been widely studied, and it has been reported that miRNAs can regulate ~1/3 of all mammalian expressing genes at the post-transcriptional level, as well as inhibiting translation and/or degrading their targeted mRNAs (8).…”

Section: Screening and Identification Of Differentially Expressed Micrornas In Diffuse Large B-cell Lymphoma Based On Microrna Microarraymentioning

confidence: 99%

Screening and identification of differentially expressed microRNAs in diffuse large B‑cell lymphoma based on microRNA microarray

Gao

Wang

et al. 2021

Oncol Lett

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Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell non-Hodgkin lymphoma in adults and the pathogenesis of DLBCL is multifactorial and complex. Understanding the molecular mechanisms involved in DLBCL is important to identify new therapeutic targets. The present study aimed to screen and identify differentially expressed microRNAs (miRNAs/miRs) between diffuse large B-cell lymphoma (DLBCL) and control [lymph node reactive hyperplasia (LRH)] groups, and to investigate whether miRNAs associated with DLBCL could serve as potential therapeutic targets. In total, 5 DLBCL experimental samples and 5 control samples were obtained from fresh patient tissues. Firstly, the fresh samples were analyzed using miRNA microarray to identify differentially expressed miRNAs. Next, three databases (TargetScan, microRNA. org and PITA) were used to predict by intersection the potential target genes of the 204 differential miRNAs identified, and a Venn diagram of the results was performed. Subsequently, the target genes of differential miRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Finally, to validate the miRNA microarray data, reverse transcription-quantitative PCR (RT-qPCR) was performed for 8 differentially expressed miRNAs (miR-193a-3p, miR-19a-3p, miR-19b-3p, miR-370-3p, miR-1275, miR-490-5p, miR-630 and miR-665) using DLBCL and LRH fresh samples. In total, 204 miRNAs exhibited differential expression, including 105 downregulated and 54 upregulated miRNAs. The cut-off criteria were set as P≤0.05 and fold-change ≥2. A total of 7,522 potential target genes for the 204 miRNAs were predicted. Potential target genes were enriched in the following pathways: 'Cancer', 'MAPK signaling pathway', 'regulation of actin cytoskeleton', 'focal adhesion', 'endocytosis', 'Wnt signaling pathway', 'axon guidance', 'calcium signaling pathway' and 'PI3K/AKT signaling pathway'. A total of 8 miRNAs were validated by ) exhibited low expression levels in DLBCL (P<0.05), while miR-630 was highly expressed in DLBCL (P<0.05). Overall, the present study screened 204 differentially expressed miRNAs and analyzed the expression levels of 8 differentially expressed miRNAs in DLBCL. These differentially expressed miRNAs may serve as therapeutic targets for improvement of therapeutic efficacy in DLBCL in the future.

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Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA

Cited by 53 publications

References 57 publications

Chemical shift prediction of RNA imino groups: application toward characterizing RNA excited states

Chemical shift prediction of RNA imino groups: application toward characterizing RNA excited states

MicroRNAs in Prion Diseases—From Molecular Mechanisms to Insights in Translational Medicine

Screening and identification of differentially expressed microRNAs in diffuse large B‑cell lymphoma based on microRNA microarray

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