In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-11-21)
Kurzfassung:
Traditionally genes are considered to contain all the instructions necessary to build proteins. For these instructions to be followed they need to be ‘transcribed’ into molecules called messenger RNA, which are then ‘translated’ to form the protein. Messenger RNAs are not the only type of RNA molecule made in a cell; long non-coding RNAs (or lncRNAs), for example, are transcribed but never translated into proteins. Instead, some lncRNAs control the expression of nearby genes and some alter how the DNA is packaged within the cell. Several lncRNAs have been found to control their neighbouring genes, but it is unclear how many of these molecules can also regulate genes that are much further away, even on other chromosomes. One lncRNA called Dali is made in cells of the nervous system of mammals. In the genome, the gene for Dali is situated next to a gene called Pou3f3, which encodes a protein that contributes to the growth and development of nerves and the kidneys. Chalei et al. have now shown that artificially reducing the amount of the Dali lncRNA restricts the development of mouse cells called N2A cells, which are commonly used to study the development of nerve cells. Reducing Dali lncRNA levels in these cells caused Pou3f3 messenger RNA levels to also decrease, which demonstrates that Dali is a lncRNA that controls its neighbouring gene. The levels of many other genes were also changed when Dali levels were reduced, including many genes that are needed to grow working nerve cells. Chalei et al. also showed that the Dali lncRNA binds to 1427 different regions of the genome of N2A cells, most often near to the start of active genes; Dali could be carried to these sites by the POU3F3 protein. The DNA sequences with which the Dali lncRNA binds were all different. Chalei et al. found that Dali also binds to an enzyme, called DNMT1, that chemically modifies DNA to change how it is packaged into a cell, and they predict that this enzyme helps Dali to find its binding sites. Furthermore, when Dali lncRNA levels were artificially reduced, the chemical modifications that affect the packaging of DNA in the cell—and hence the expression of genes encoded by this DNA—were changed for several genes. Some of these genes were located far away from the gene that encodes Dali, indicating that this lncRNA can regulate the packaging and expression of distant genes. Many genes that are regulated by Dali are also regulated by the POU3F3 protein; this suggests that the lncRNA might work together with this protein to affect the expression of some genes. Further work is now needed to uncover how many other lncRNAs act away from their sites of synthesis, and how many also form complexes with DNA-binding and DNA-modifying proteins.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.04530.001
DOI:
10.7554/eLife.04530.002
DOI:
10.7554/eLife.04530.003
DOI:
10.7554/eLife.04530.004
DOI:
10.7554/eLife.04530.005
DOI:
10.7554/eLife.04530.006
DOI:
10.7554/eLife.04530.007
DOI:
10.7554/eLife.04530.008
DOI:
10.7554/eLife.04530.009
DOI:
10.7554/eLife.04530.010
DOI:
10.7554/eLife.04530.011
DOI:
10.7554/eLife.04530.012
DOI:
10.7554/eLife.04530.013
DOI:
10.7554/eLife.04530.014
DOI:
10.7554/eLife.04530.015
DOI:
10.7554/eLife.04530.016
DOI:
10.7554/eLife.04530.017
DOI:
10.7554/eLife.04530.018
DOI:
10.7554/eLife.04530.019
DOI:
10.7554/eLife.04530.020
DOI:
10.7554/eLife.04530.021
DOI:
10.7554/eLife.04530.022
DOI:
10.7554/eLife.04530.023
DOI:
10.7554/eLife.04530.024
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2014
ZDB Id:
2687154-3
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