Clustering and conservation patterns of human microRNAs

By Yael Altuvia, Pablo Landgraf, G. Lithwick, Naama Elefant, S. Pfeffer, Alexei Aravin, M. Brownstein, Thomas Tuschl, Hanah Margalit. Nucleic Acids Research, 2005

842 citations recorded by the source corpus.

MicroRNAs (miRNAs) are ∼22 nt-long non-coding RNA molecules, believed to play important roles in gene regulation. We present a comprehensive analysis of the conservation and clustering patterns of known miRNAs in human. We show that human miRNA gene clustering is significantly higher than expected at random. A total of 37% of the known human miRNA genes analyzed in this study appear in clusters of two or more with pairwise chromosomal distances of at most 3000 nt. Comparison of the miRNA sequences with their homologs in four other organisms reveals a typical conservation pattern, persistent throughout the clusters. Furthermore, we show enrichment in the typical conservation patterns and other miRNA-like properties in the vicinity of known miRNA genes, compared with random genomic regions. This may imply that additional, yet unknown, miRNAs reside in these regions, consistent with the current recognition that there are overlooked miRNAs. Indeed, by comparing our predictions with cloning results and with identified miRNA genes in other mammals, we corroborate the predictions of 18 additional human miRNA genes in the vicinity of the previously known ones. Our study raises the proportion of clustered human miRNAs that are <3000 nt apart to 42%. This suggests that the clustering of miRNA genes is higher than currently acknowledged, alluding to its evolutionary and functional implications.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3f3757499affd63e5eb65f49541f38043275a047

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Citations in the corpus

Conservation and divergence of plant microRNA genes. (2006, background): “Accumulating evidence in animals suggests that clustered miRNAs have similar gene expression patterns and are transcribed together as a polycistron (Altuvia et al., 2005; Bartel, 2004; Baskerville and Bartel, 2005).”
Role of microRNAs in vascular diseases, inflammation, and angiogenesis. (2008, background): “MiRNAs that have their own promoters are independently expressed, and miRNAs organized in clusters share the same transcriptional regulation.(3,4) Once the miRNAs are expressed, their maturation is mediated by the two RNase III endonucleases Dicer and Drosha (Figure 1; for review see(5)).”
The Role of MicroRNAs in Human Diseases (2010, background): “In the genome, miRNAs are organized in clusters and share the same transcriptional regulatory units and are independently expressed if they have their own promoters (24, 25) .”
MicroRNA: Biogenesis, Function and Role in Cancer (2010, background): “Recent genomic analysis indicates that primary miRNA precursors are long polycistronic transcripts that are similar to mRNA in that they have distinct 5’ and 3’ boundaries, 7-methyl guanylate (m7G) caps and poly(A) tails [12, 38-41].”
Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. (2006, background): “31 (Altuvia et al., 2005), recent studies have revealed that miR-127 and miR-136 have different expression patterns in human cancers (Iorio et al., 2005; Lu et al., 2005).”
Exosomal cell-to-cell transmission of alpha synuclein oligomers (2012, neutral): “431 CNS specific miRNA [47,50]”
Plant microRNA: a small regulatory molecule with big impact. (2006, background): “(3) Many miRNAs are evolutionarily conserved, some from worm to human (Weber, 2005; Berezikov et al., 2005; Altuvia et al., 2005), or from ferns to core eudicots or monocots in plants (Reinhart et al.”
Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network (2007, methodology): “In a previous study, which was based on 207 miRs (compared with the 461 used here), miRs were clustered using a different cutoff [49].”