Monday, 2 April 2012

Long ncRNA (Courtney Carter)


Long Non-Coding RNA:
One man’s “junk” is another man’s treasure

The focus of this blog is a study which investigated the enhancer function of long non-coding RNAs in human cells.  It achieved multiple ratings of 10/10 from Faculty of 1000, rendering it a must read.
A Little Background
As we know, RNAs are sequences of nucleotides responsible for gene expression.  The primary function of RNA is commonly understood to be converting genetic information from DNA into physical proteins through synthesis or encryption of messenger-RNA molecules (mRNA).  However, mRNA is not the only form and function of RNA involved in gene expression.  In fact, whilst most DNA is transcribed into RNA, only a small portion of these are for protein synthesis.  A substantial group of RNA molecules are non-coding RNA (ncRNA) which have typically been discarded as “junk”. Until now.
There are several different types of ncRNAs which come from intergenic and intronic DNA, one of which are long ncRNAs.  Long ncRNAs are non-coding molecules which consist of more than one hundred nucleotides, and are the focus of the paper evaluated in F1000.
Finding the Long ncRNAs
The researchers systematically identified the long ncRNAs, excluding DNA overlapping with protein-coding genes and already classified RNA.  They identified over 1000 new long ncRNAs with individual patterns of expression.  The average size of these long ncRNAs was about 800 nucleotides, ranging from 100 to a whopping 9100 nucleotides.  They found evidence of about 80% of the long ncRNAs in at least one human tissue.
Determining the Function
The researchers used a small interfering RNA (siRNA) or silencing RNA to interfere with the expression of the long ncRNAs in particular DNA strands.  Initially, they observed that this depletion of the long ncRNAs resulted in decreased expression of the surrounding ECM1 genes.  The researchers then depleted the ECM1 gene with siRNA but the ncRNA expression did not decrease, indicating that the two transcriptions were independent units, and that the long ncRNA independently regulated the EMC1 gene’s expression.

Next, the researchers tried to ascertain whether the long ncRNA’s role as an enhancer was a common function, by investigating the effect of depleting long ncRNAs in proximity to the stem-cell leukemia gene (TAL1).  For those unaware, leukemia is a disease characterised by the production of too many immature white blood cells, resulting in an inability for the cells to mature.  The TAL1 gene regulates hematopoiesis, or the formation of cellular components of blood.  The researchers again found that, “depletion of ncRNA resulted in a specific and potent reduction of TAL1 expression,” further solidifying the long ncRNA’s function as an enhancer for gene expression.
It seems to me that this finding could have massive implications.  In the immediate context of this study, the fact that synthetic depletion of adjacent long ncRNA decreased the expression of the TAL1 gene means that leukemia originating from this gene could be set back by limiting the long ncRNAs proximal to it.  In the general sense, increasing the prevalence of long ncRNA near useful genes and depleting long ncRNA near problematic genes could provide a remedy for a wide range of medical disorders.
Courtney Carter - 42008622

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