Skip to content

Researchers begin to map function and expression of isomiRs of microRNA.

Researchers have encountered variants or isoforms in microRNAs (miRNAs) before, but assumed that these variants were accidental byproducts. A recent study from Thomas Jefferson University shows that certain so called isomiRs have abundances that depend on geographic subpopulations and gender and that the most prevalent variant of a given miRNA may not be the one typically listed in the public databases. The study is published in the journal Oncotarget.

The study shows that microRNA isoforms are much more common than the medical community had previously assumed. The fact that some isoforms are shared by certain subpopulations or are more prominent in women than in men suggests that their presence likely serves a purpose and this warrants further study.

MiRNAs are short non-coding RNAs approximately 22 nucleotides in length that were first discovered a little over 20 years ago. It was not long after their discovery that they began commanding the attention of many researchers worldwide thanks to their intimate involvement in many cellular events. Researchers know now that miRNAs are regulators of protein-coding and also of non-protein-coding RNA transcripts and that they regulate the abundance of the affected transcripts, the miRNA targets, in a sequence-dependent manner. What makes miRNAs so important is their involvement in fundamental processes such as development and homeostasis. Not surprisingly, miRNAs and their dysregulation have also being linked to many human conditions, diseases, and syndromes.

MiRNAs, just like the messenger RNAs that code for proteins, have isoforms i.e. variants that arise from the same genomic locus and differ from one another by only 1-2 letters at either their left or right terminus. Different variants of a given miRNA typically have different abundances compared to that of the ‘representative’ isoform of the locus which is also the one that is generally listed in the public databases.

For many years, miRNA isoforms had been thought of as inconsequential. However, the advent of next generation sequencing, or deep sequencing, is now enabling scientists to take a higher-resolution look at these molecular events.

In the current study, the team analyzed deep sequencing data from lymphoblastoid cell lines (LCLs) derived from 452 men and women from five different population groups capturing four European and one African ancestries. The team discovered that the isomiRs in these LCLs exhibit expression profiles that are population-dependent and gender-dependent with differences existing even among the European populations.

By analyzing independently obtained experimental data, the team was able to generate additional evidence showing that many of the isomiRs they identified could also associate with the Argonaute silencing complex, suggesting that these miRNA variants participate in the RNA interference pathway and have functional roles just like the ‘representative’ miRNA from the corresponding locus. What these functional roles are and how they differ for each variant is only beginning to be understood. Even though the team worked with LCLs, analogous observations likely hold true for other cell types as well.

The team’s findings have several implications. For researchers they suggest that the assays currently in the market do not necessarily capture the variant that is prevalent in the cells with which a researcher works, instead measuring a less abundant isoform that is perhaps nonessential for the cell or tissue type at hand.

The findings suggest that even cell lines from the same tissue could have more differences than they have similarities. For patients, the findings represent an opportunity for a potentially significant advantage, the knowledge that a given patient has a different molecular profile than another patient with the same disease is a very important piece of information that physicians can use to the patient’s benefit when deciding which course of medical treatment to follow.

Source:  Thomas Jefferson University (TJU)

 

Differential expression of isomiRs across populations.  Using samples from both genders, the team identified differentially expressed isomiRs separately for each pair of populations. This figure shows the resulting heat-map for the identified isomiRs. Cells shown in light gray correspond to cases that did not reach statistical significance for the corresponding isomiR/population combination. All other cells correspond to statistically significant combinations with an associated FDR value ≤ 0.05. The color intensity scale is logarithmic (log2 base).  Note that the Fig. depicts redundant information in that all 5x4 population pairs are shown.  IsomiR expression profiles in human lymphoblastoid cell lines exhibit population and gender dependencies.  Rigoutsos et al 2014.
Differential expression of isomiRs across populations. Using samples from both genders, the team identified differentially expressed isomiRs separately for each pair of populations. This figure shows the resulting heat-map for the identified isomiRs. Cells shown in light gray correspond to cases that did not reach statistical significance for the corresponding isomiR/population combination. All other cells correspond to statistically significant combinations with an associated FDR value ≤ 0.05. The color intensity scale is logarithmic (log2 base). Note that the Fig. depicts redundant information in that all 5×4 population pairs are shown. IsomiR expression profiles in human lymphoblastoid cell lines exhibit population and gender dependencies. Rigoutsos et al 2014.

Healthinnovations View All

Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.

Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.

Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

2 thoughts on “Researchers begin to map function and expression of isomiRs of microRNA. Leave a comment

  1. Hey, good morning. Interesting article. You have gained a new reader. Pleasee maintain up the excellent work and I look forward to much more of your brilliant articles. God bless, .

Leave a Reply

Translate »