Long non coding RNAs approaching the title of the Almighty
For the uninitiated, long non coding RNAs are molecules within cells, which are rule-breakers; they do not code for proteins, and defy the central dogma. The central dogma dictates that all information required to make a cell, a tissue, an organ or an individual as a whole is stored in the genetic material or DNA, which is transcribed to RNA, finally translated to proteins- the building blocks that form the cells.
Several projects have been undertaken by scientists to understand the DNA or the genome. The ENCODE project opened up the possibility of pervasive transcription across eukaryotic genomes. A closer look divulged the most abundant of the transcribed junk DNA, dubbed the long non coding RNA (lncRNA). Over the past couple of decades, this multitude of transcripts has been attributed a wide range of functions.
But what sets apart these transcripts from the protein coding messenger RNAs (mRNAs)? Besides the obvious fact that they do not encode proteins, they exhibit restricted spatio- temporal expression patterns and less abundant levels in comparison with mRNAs. These are considered hallmarks of lncRNAs.
For readers familiar with the field, it is a commonly known fact that more often than not, a lncRNA research report commences with a statement fashioned in different ways: "The functions of this ambiguous class of transcripts are still mostly unexplored." Incidentally, as the literature around lncRNAs has reached over thousands of research reports, it seems that a handful of them have achieved some sort of "super" regulational abilities. They seem to be expressed in every other tissue type, cell type, are differentially regulated in disease conditions ranging from genetic to metabolic to infectious and are potent biomarkers for each of the described conditions. While these reports are in the most respected journals and leave no doubt are authentic, this is a clear case of trail- chasing with very little emphasis on curiosity driven studies. The accumulation of iterative studies with a change in context or tweaking of conditions will lead to saturation of the field with mirror- image research, and very little progress in understanding the entirety of lncRNA- mediated regulation.
For instance, let me explain the exercise I performed with one of the "super" lncRNAs. When I entered MALAT1 into the search tab of the PubMed portal (Accessed 12:44 PM 3rd February 2019, IST), the search yielded 803 results, a mix of research reports and reviews. The 803 reports were published across a span of roughly 13 years. The number of articles pertaining to MALAT1 that were published in the month of January 2019 alone was 17. I added a keyword "Cancer", and the number of hits were 505. Isn't it quite impressive that a single lncRNA could be the one stop answer for so many biological conditions? Next, I went to the recent and 'not-peer-reviewed' database: The Biorxiv (Accessed 1:02 PM 3rd February 2019, IST). I searched "MALAT1". The number of hits that showed up were 142.
The blessing with the digital era is this transparency and the availability of a holistic picture of the research on a single transcript, among many thousands of similar ones. One could repeat the exercise with other almighty lncRNAs such as HOTAIR, NEAT1, MEG3, H19, ANRIL, MIAT, and find similar results. This list is definitely growing, and the over- representation of each almighty lncRNA certainly dwindling, but not impressively enough.
To reemphasize, while none of these studies are questionable, the spirit in which they were performed isn't very encouraging. Given that technologies to identify novel transcripts at even single- cell level and high throughput genome editing techniques facilitating convenient functional annotation have been picking pace along the past few years, it is only fair to expect that lncRNA researchers take up more of curiosity driven research. We could keep growing horizontally, but going vertically wouldn't be too bad either. It is the 21st century, after all.
Several projects have been undertaken by scientists to understand the DNA or the genome. The ENCODE project opened up the possibility of pervasive transcription across eukaryotic genomes. A closer look divulged the most abundant of the transcribed junk DNA, dubbed the long non coding RNA (lncRNA). Over the past couple of decades, this multitude of transcripts has been attributed a wide range of functions.
But what sets apart these transcripts from the protein coding messenger RNAs (mRNAs)? Besides the obvious fact that they do not encode proteins, they exhibit restricted spatio- temporal expression patterns and less abundant levels in comparison with mRNAs. These are considered hallmarks of lncRNAs.
For readers familiar with the field, it is a commonly known fact that more often than not, a lncRNA research report commences with a statement fashioned in different ways: "The functions of this ambiguous class of transcripts are still mostly unexplored." Incidentally, as the literature around lncRNAs has reached over thousands of research reports, it seems that a handful of them have achieved some sort of "super" regulational abilities. They seem to be expressed in every other tissue type, cell type, are differentially regulated in disease conditions ranging from genetic to metabolic to infectious and are potent biomarkers for each of the described conditions. While these reports are in the most respected journals and leave no doubt are authentic, this is a clear case of trail- chasing with very little emphasis on curiosity driven studies. The accumulation of iterative studies with a change in context or tweaking of conditions will lead to saturation of the field with mirror- image research, and very little progress in understanding the entirety of lncRNA- mediated regulation.
For instance, let me explain the exercise I performed with one of the "super" lncRNAs. When I entered MALAT1 into the search tab of the PubMed portal (Accessed 12:44 PM 3rd February 2019, IST), the search yielded 803 results, a mix of research reports and reviews. The 803 reports were published across a span of roughly 13 years. The number of articles pertaining to MALAT1 that were published in the month of January 2019 alone was 17. I added a keyword "Cancer", and the number of hits were 505. Isn't it quite impressive that a single lncRNA could be the one stop answer for so many biological conditions? Next, I went to the recent and 'not-peer-reviewed' database: The Biorxiv (Accessed 1:02 PM 3rd February 2019, IST). I searched "MALAT1". The number of hits that showed up were 142.
The blessing with the digital era is this transparency and the availability of a holistic picture of the research on a single transcript, among many thousands of similar ones. One could repeat the exercise with other almighty lncRNAs such as HOTAIR, NEAT1, MEG3, H19, ANRIL, MIAT, and find similar results. This list is definitely growing, and the over- representation of each almighty lncRNA certainly dwindling, but not impressively enough.
To reemphasize, while none of these studies are questionable, the spirit in which they were performed isn't very encouraging. Given that technologies to identify novel transcripts at even single- cell level and high throughput genome editing techniques facilitating convenient functional annotation have been picking pace along the past few years, it is only fair to expect that lncRNA researchers take up more of curiosity driven research. We could keep growing horizontally, but going vertically wouldn't be too bad either. It is the 21st century, after all.
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