Automatically clustering large-scale miRNA sequences: methods and experiments

<p>Abstract</p> <p>Background</p> <p>Since the initial annotation of microRNAs (miRNAs) in 2001, many studies have sought to identify additional miRNAs experimentally or computationally in various species. MiRNAs act with the Argonaut family of proteins to regulate target messenger RNAs (mRNAs) post-transcriptionally. Currently, researches mainly focus on single miRNA function study. Considering that members in the same miRNA family might participate in the same pathway or regulate the same target(s) and thus share similar biological functions, people can explore useful knowledge from high quality miRNA family architecture.</p> <p>Results</p> <p>In this article, we developed an unsupervised clustering-based method miRCluster to automatically group miRNAs. In order to evaluate this method, several data sets were constructed from the online database miRBase. Results showed that miRCluster can efficiently arrange miRNAs (e.g identify 354 families in miRBase16 with an accuracy of 92.08%, and can recognize 9 of all 10 newly-added families in miRBase 17). By far, ~30% mature miRNAs registered in miRBase are unclassified. With miRCluster, over 85% unclassified miRNAs can be assigned to certain families, while ~44% of these miRNAs distributed in ~300novel families.</p> <p>Conclusions</p> <p>In short, miRCluster is an automatic and efficient miRNA family identification method, which does not require any prior knowledge. It can be helpful in real use, especially when exploring functions of novel miRNAs. All relevant materials could be freely accessed online (<url>http://admis.fudan.edu.cn/projects/miRCluster</url>).</p

A non-coding function of TYRP1 mRNA promotes melanoma growth

International audienceCompetition among RNAs to bind miRNA is proposed to influence biological systems. However, the role of this competition in disease onset is unclear. Here, we report that TYRP1 mRNA, in addition to encoding tyrosinase-related protein 1 (TYRP1), indirectly promotes cell proliferation by sequestering miR-16 on non-canonical miRNA response elements. Consequently, the sequestered miR-16 is no longer able to repress its mRNA targets, such as RAB17, which is involved in melanoma cell proliferation and tumour growth. Restoration of miR-16 tumour-suppressor function can be achieved in vitro by silencing TYRP1 or increasing miR-16 expression. Importantly, TYRP1-dependent miR-16 sequestration can also be overcome in vivo by using small oligonucleotides that mask miR-16-binding sites on TYRP1 mRNA. Together, our findings assign a pathogenic non-coding function to TYRP1 mRNA and highlight miRNA displacement as a promising targeted therapeutic approach for melanoma