In this interview Dr Isidore Rigoutsos discusses his recent paper ‘Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs‘ published in PNAS, February 2015. This paper shows the presence of many more miRNAs than previously thought and uncovers that the majority of these are in fact, cell-type and species specific.
Dr Rigoutsos is the Director of the Computational Medicine Center at Thomas Jefferson University. He also has joint appointments in the Department of Cancer Biology, and the Department of Biochemistry & Molecular Biology. Previously, he worked at IBM’s Thomas J. Watson Research Center where he founded and managed the Bioinformatics and Pattern Discovery group. He has a particular interest in studying non-coding RNAs (microRNAs, piRNAs, etc.).
More miRNAs Than You Can Count
Dr Isidore Rigoutsos discusses how he got involved in studying miRNAs and his research published in Cell, 2006 which indicated that the likely number of miRNA precursors is much higher than previously thought, with over >25,000 likely miRNA precursors in humans. He also describes how the advent of deep sequencing and the increase in availability of deep sequencing datasets has allowed him and his team to revisit the question of how many miRNAs exist in the humans. In this recent paper he finds 3,707 novel miRNAs based on sampling just 13 tissue types and believes that larger sampling would uncover many more miRNAs.
Hidden in Plain Sight: Why Haven’t We Uncovered More miRNAs Before?
Why this wealth of miRNAs hasn’t been uncovered before is down to the simple fact that people haven’t looked! In the past it has been considered that in order for an miRNA to be considered real, it has to be expressed across cell types and different organisms. By relaxing this constraint Isidore and his lab were able to uncover the true vastness of miRNAs and that many are tissue type specific.
Setting us Apart From the Apes: Species Specificity of miRNAs
From their research the lab found that a whopping 95% of the novel miRNAs uncovered were primate specific and of these 55% were specific to humans.
Novel Seed Sequences: a Consequence of Species Specificity?
In addition to uncovering novel miRNAs, analysis of these new miRNAs indicates the presence of 888 novel seed sequences. Isidore talks about whether this is a likely consequence of the species and cell type specificity of these new miRNAs and that in order to answer this wee need to look more deeply at other organisms to determine if these seeds are present.
In addition, he touches upon how our understanding of how miRNAs interact with targets, how our definition of what defines a miRNA has changed and how this knowledge is changing the way we uncover targets of miRNA. He highlights that while seed sequence is a strong definer of a family, it doesn’t necessarily indicate a target, given that there have already been examples where miRNAs with the same seed target different targets.
The New Mass of miRNAs: Significant or Superfluous?
The uncovering of the new wealth of miRNAs means there is still more work to go, but Isidore mentions that this has possible benefits for studying different tissues and also suggests that miRNAs may have more of a role in disease and that investigating these miRNAs may help understand the biology of difference diseases.
How many Graduate Students Does it Take to Understand miRNAs?
If we work on the equation of one miRNA per graduate student project we are going to have to have many more students in order to understand each of these new miRNAs. New datasets and deep sequencing will certainly help progress the field, but in the end understanding the targets and functions of individual miRNAs all comes down to manpower.
Listen to the full interview with Isidore.