I am a scientist specialized in genetics and metabolism.


Who would have thought junk could be so useful...

In 10 seconds? Over 98% of our genome does not code for any genes and was believed to have no biological function. But recent research has shown that this “junk DNA” plays an essential role in development and disease.

How can noncoding DNA have any impact on development? Although noncoding DNA does not code for any protein, most of it is transcripted to RNA. In fact, the Encyclopaedia of DNA Elements (ENCODE) project has shown that around 80% of noncoding DNA is transcripted and that this RNA plays an important part in the epigenetic control of gene expression, being involved in almost all cellular processes.

What kind of RNA are we talking about? Noncoding RNA (ncRNA) has multiple forms: microRNA (miRNA), small-interfering RNA (siRNA) and P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA), which are short and negatively regulate gene expression by aiming mRNA and inactivating or degrading it; and long non-coding RNAs (lncRNAs) which are more complex and affect both positively and negatively gene expression.

Why is long noncoding RNA more complex? lncRNAs share several features with coding transcripts, such as differential expression due to epigenetic regulation, and the presence of introns and splice variants. Thus, their expression, and therefore function, can be highly diverse. For example, they can inhibit miRNAs, thereby boosting the expression of the gene regulated by them; they can also directly activate transcription of neighboring genes, such as enhancer RNAs (eRNAs) and activating ncRNAs (ncRNA-as); or inhibit gene expression by targeting mRNA for degradation or inactivating transcription, such as the X-chromosome inactivation (XIST) lncRNA, responsible for silencing regions of the X chromosome, such that only one copy of a given gene of this chromosome is expressed.

And what function do they have on development and disease? Although the function of most noncoding RNAs remains to be determined, they have been shown to play an important role in spatiotemporal and cell-type specific gene expression, regulating cell growth and differentiation, and therefore in several diseases, such as cancer, like the noncoding RNA CASC2, a potential tumor suppressor.


Non-coding RNAs as regulators in epigenetics (Review).

Abstract: Epigenetics is a discipline that studies heritable changes in gene expression that do not involve altering the DNA sequence. Over the past decade, researchers have shown that epigenetic regulation plays a momentous role in cell growth, differentiation, autoimmune diseases, and cancer. The main epigenetic mechanisms include the well-understood phenomenon of DNA methylation, histone modifications, and regulation by non-coding RNAs, a mode of regulation that has only been identified relatively recently and is an area of intensive ongoing investigation. It is generally known that the majority of human transcripts are not translated but a large number of them nonetheless serve vital functions. Non-coding RNAs are a cluster of RNAs that do not encode functional proteins and were originally considered to merely regulate gene expression at the post-transcriptional level. However, taken together, a wide variety of recent studies have suggested that miRNAs, piRNAs, endogenous siRNAs, and long non-coding RNAs are the most common regulatory RNAs, and, significantly, there is a growing body of evidence that regulatory non-coding RNAs play an important role in epigenetic control. Therefore, these non-coding RNAs (ncRNAs) highlight the prominent role of RNA in the regulation of gene expression. Herein, we summarize recent research developments with the purpose of coming to a better understanding of non-coding RNAs and their mechanisms of action in cells, thus gaining a preliminary understanding that non-coding RNAs feed back into an epigenetic regulatory network.

Pub.: 15 Nov '16, Pinned: 24 Jun '17

Origin and evolution of the metazoan non-coding regulatory genome.

Abstract: Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal and cell-type specific gene expression that is essential for the development and maintenance of a multicellular lifestyle. Although it is widely appreciated that these systems ultimately evolved from genomic regulatory mechanisms present in single-celled stem metazoans, it remains unclear how this occurred. Here, we focus on the contribution of the non-coding portion of the genome to the evolution of animal gene regulation, specifically on recent insights from non-bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa. High-throughput next-generation sequencing, largely in bilaterian model species, has led to the discovery of tens of thousands of non-coding RNA genes (ncRNAs), including short, long and circular forms, and uncovered the central roles they play in development. Based on the analysis of non-bilaterian metazoan, unicellular holozoan, and fungal genomes, the evolution of some ncRNAs, such as Piwi-interacting RNAs, correlates with the emergence of metazoan multicellularity, while others, including microRNAs, long non-coding RNAs, and circular RNAs, appear to be more ancient. Analysis of non-coding regulatory DNA and histone post-translational modifications have revealed that some cis-regulatory mechanisms, such as those associated with proximal promoters, are present in non-animal holozoans while others appear to be metazoan innovations, most notably distal enhancers. In contrast, the cohesin-CTCF system for regulating higher-order chromatin structure and enhancer-promoter long-range interactions appears to be restricted to bilaterians. Taken together, most bilaterian non-coding regulatory mechanisms appear to have originated before the divergence of crown metazoans. However, differential expansion of non-coding RNA and cis-regulatory DNA repertoires in bilaterians may account for their increased regulatory and morphological complexity relative to non-bilaterians.

Pub.: 24 Nov '16, Pinned: 24 Jun '17