Impact of host genes and strand selection on miRNA and miRNA* expression

Marta Biasiolo, Gabriele Sales, Marta Lionetti, Luca Agnelli, Katia Todoerti, Andrea Bisognin, Alessandro Coppe, Chiara Romualdi, Antonino Neri, Stefania Bortoluzzi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Dysregulation of miRNAs expression plays a critical role in the pathogenesis of genetic, multifactorial disorders and in human cancers. We exploited sequence, genomic and expression information to investigate two main aspects of post-transcriptional regulation in miRNA biogenesis, namely strand selection regulation and expression relationships between intragenic miRNAs and host genes. We considered miRNAs expression profiles, measured in five sizeable microarray datasets, including samples from different normal cell types and tissues, as well as different tumours and disease states. First, the study of expression profiles of "sister" miRNA pairs (miRNA/miRNA*, 5′ and 3′ strands of the same hairpin precursor) showed that the strand selection is highly regulated since it shows tissue-/cell-/condition-specific modulation. We used information about the direction and the strength of the strand selection bias to perform an unsupervised cluster analysis for the sample classification evidencing that is able to distinguish among different tissues, and sometimes between normal and malignant cells. Then, considering a minimum expression threshold, in few miRNA pairs only one mature miRNA is always present in all considered cell types, whereas the majority of pairs were concurrently expressed in some cell types and alternatively in others. In a significant fraction of concurrently expressed pairs, the major and the minor forms found at comparable levels may contribute to post-transcriptional gene silencing, possibly in a coordinate way. In the second part of the study, the behaved tendency to co-expression of intragenic miRNAs and their "host" mRNA genes was confuted by expression profiles examination, suggesting that the expression profile of a given host gene can hardly be a good estimator of co-transcribed miRNA(s) for post-transcriptional regulatory networks inference. Our results point out the regulatory importance of post-transcriptional phases of miRNAs biogenesis, reinforcing the role of such layer of miRNA biogenesis in miRNA-based regulation of cell activities.

Original languageEnglish
Article numbere23854
JournalPLoS One
Volume6
Issue number8
DOIs
Publication statusPublished - 2011

Fingerprint

MicroRNAs
microRNA
Genes
genes
cells
Tissue
neoplasms
RNA interference
cluster analysis
Inborn Genetic Diseases
pathogenesis
Selection Bias
Gene Regulatory Networks
Cluster analysis
Microarrays
taxonomy
genomics
RNA Interference
sampling
Cluster Analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Impact of host genes and strand selection on miRNA and miRNA* expression. / Biasiolo, Marta; Sales, Gabriele; Lionetti, Marta; Agnelli, Luca; Todoerti, Katia; Bisognin, Andrea; Coppe, Alessandro; Romualdi, Chiara; Neri, Antonino; Bortoluzzi, Stefania.

In: PLoS One, Vol. 6, No. 8, e23854, 2011.

Research output: Contribution to journalArticle

Biasiolo, M, Sales, G, Lionetti, M, Agnelli, L, Todoerti, K, Bisognin, A, Coppe, A, Romualdi, C, Neri, A & Bortoluzzi, S 2011, 'Impact of host genes and strand selection on miRNA and miRNA* expression', PLoS One, vol. 6, no. 8, e23854. https://doi.org/10.1371/journal.pone.0023854
Biasiolo, Marta ; Sales, Gabriele ; Lionetti, Marta ; Agnelli, Luca ; Todoerti, Katia ; Bisognin, Andrea ; Coppe, Alessandro ; Romualdi, Chiara ; Neri, Antonino ; Bortoluzzi, Stefania. / Impact of host genes and strand selection on miRNA and miRNA* expression. In: PLoS One. 2011 ; Vol. 6, No. 8.
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