isomiRdb: microRNA expression at isoform resolution

Aparicio‐Puerta, Ernesto; Hirsch, Pascal; Schmartz, Georges Pierre; Fehlmann, Tobias; Keller, Verena; Engel, Annika; Kern, Fabian; Hackenberg, Michael; Keller, Andreas

doi:10.1093/nar/gkac884

Cited by 14 publications

(16 citation statements)

References 38 publications

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“…These variants, known as isomiRs, are reported to have different turnover rates [4,34]. Interestingly, using the isomiRdb database [15], we found that two noncanonical isomiRs of miR‐133a (5′‐end trimmed and 3′‐end U‐tailed, and 3′‐end U‐tailed) are more abundant than its canonical isoform in muscle (Fig. 5A), whereas the most abundant isomiR of miR‐1 is the canonical isoform (Fig.…”

Section: Discussionmentioning

confidence: 96%

“…Because miR-1 had a short half-life in our dataset, we assumed it to have a quite high turnover rate. MiR-206 is a skeletal-muscle-specific miRNA belonging to the same miRNA family as miR-1 [27] that shares sequences identical to those of miR-1, including the seed sequences and an additional supplementary pairing region (nucleotides [13][14][15][16]. Several miRNA families that share seed sequences have been shown to have similar decay rates in mouse fibroblasts [4].…”

Section: Discussionmentioning

confidence: 99%

“…We analyzed the expression data for the hsa-miR-133a-3p and hsa-miR-1-3p isoforms (isomiRs) in muscle. The expression profiles of each isomiR for miR-133a and miR-1 were collected from isomiRdb [15], and reconstituted in the figure (Fig. 5).…”

Section: Metabolic Turnover Of Mirnas and Mrnas In Differentiated C2c...mentioning

confidence: 99%

“…The expression data for the hsa-miR-133a-3p and hsa-miR-1-3p isoforms (isomiRs) in muscle were collected from isomiRdb (https://ccb-compute.cs.uni-saarland.de/isomirdb) [15] and reconstituted. The data are presented as the mean log 10 (reads per million [RPM] + 1).…”

Section: Analysis Of Isomir Expressionmentioning

confidence: 99%

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Skeletal muscle‐enriched miRNAs are highly unstable in vivo and may be regulated in a Dicer‐independent manner

et al. 2023

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MicroRNAs (miRNAs) are small noncoding RNAs that control essential cellular processes. For several decades, the molecular mechanisms underlying the functions and biogenesis of miRNAs have been clarified, whereas the molecular dynamics of miRNAs are poorly understood. We recently found that muscle‐enriched miRNAs were reduced by only 20~50% in the skeletal muscles even 4 weeks after the suppression of miRNA processing through an inducible depletion of Dicer1 gene. These data suggest that miRNAs are stably expressed in skeletal muscle. In this study, we investigated the half‐lives of those miRNAs in adult skeletal muscle with an in vivo metabolic labeling strategy and a genetic mouse model. In contrast to the hypothesis, in vivo metabolic labeling revealed that the half‐lives of skeletal‐muscle‐enriched miRNAs were approximately 11‐20 hours. Furthermore, the levels of mature miR‐23a decreased rapidly in the skeletal muscle of mice lacking miR‐23 clusters in a tamoxifen‐inducible manner. These data suggest that skeletal‐muscle‐enriched miRNAs are not highly stable in vivo. We also observed that the transfer of miR‐150 into Dicer1‐deficient muscle increased the miR‐150 level to the same as that in control muscle. Taken together, our data demonstrate that miRNAs are degraded within a few days in adult skeletal muscle and that a Dicer‐independent biogenetic pathway may produce mature miRNAs.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Metabolic Turnover Of Mirnas and Mrnas In Differentiated C2c...mentioning

confidence: 99%

Section: Analysis Of Isomir Expressionmentioning

confidence: 99%

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Skeletal muscle‐enriched miRNAs are highly unstable in vivo and may be regulated in a Dicer‐independent manner

et al. 2023

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“…The mechanisms behind isomiR formation have, in general, been revealed: beside the subtle regulation of the main miRNA processing enzymes (Drosha and Dicer), the action of terminal nucleotidyl transferases, exoribonucleases and RNA editing enzymes are also responsible for the existence of certain isomiR groups (Tomasello et al 2021). On the other hand, the regulation of cell-type specific isomiR distribution is still not completely understood and this aspect is currently in the focus of intensive investigations (Zelli et al 2021;Aparicio-Puerta et al 2023). Nevertheless, isomiRs should definitely be considered in miRNA target predictions (Ahmed et al 2014), as well as in the development of new diagnostic tools and in planned therapy applications (Nikolova et al 2021;Scheper et al 2022).…”

Section: Formation Of Isomirs-substantially Increasing the Mirna Repe...mentioning

confidence: 99%

One locus, several functional RNAs—emerging roles of the mechanisms responsible for the sequence variability of microRNAs

Orbán

2023

BIOLOGIA FUTURA

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With the development of modern molecular genetics, the original “one gene-one enzyme” hypothesis has been outdated. For protein coding genes, the discovery of alternative splicing and RNA editing provided the biochemical background for the RNA repertoire of a single locus, which also serves as an important pillar for the enormous protein variability of the genomes. Non-protein coding RNA genes were also revealed to produce several RNA species with distinct functions. The loci of microRNAs (miRNAs), encoding for small endogenous regulatory RNAs, were also found to produce a population of small RNAs, rather than a single defined product. This review aims to present the mechanisms contributing to the astonishing variability of miRNAs revealed by the new sequencing technologies. One important source is the careful balance of arm selection, producing sequentially different 5p- or 3p-miRNAs from the same pre-miRNA, thereby broadening the number of regulated target RNAs and the phenotypic response. In addition, the formation of 5', 3' and polymorphic isomiRs, with variable end and internal sequences also leads to a higher number of targeted sequences, and increases the regulatory output. These miRNA maturation processes, together with other known mechanisms such as RNA editing, further increase the potential outcome of this small RNA pathway. By discussing the subtle mechanisms behind the sequence diversity of miRNAs, this review intends to reveal this engaging aspect of the inherited “RNA world”, how it contributes to the almost infinite molecular variability among living organisms, and how this variability can be exploited to treat human diseases.

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