New technique gives precise picture of how regulatory RNA controls gene activity

LincRNAs (long intergenic non-coding RNAs) seem to be the flavor du jour for researchers studying the many functions of various types of RNA, in addition to the traditional role of carrying genetic information from DNA to the cellular structures where proteins are made. Very recent research showed that lincRNAs regulate gene expression in embryonic stem cells. Another lab has now come up with a technique for determining exactly where on a cell’s chromosones a given lincRNA binds in order to regulate gene expression.

New Stanford technique gives precise picture of how regulatory RNA controls gene activity – Stanford University

A new technique developed by researchers at the Stanford University School of Medicine allows researchers to identify the exact DNA sequences and locations bound by regulatory RNAs. This information is necessary to understand how the recently identified RNA molecules control the expression of neighboring and distant genes.

The study offers a startling glimpse into the intricate world of gene expression and how RNA, once thought to be only a lowly cellular messenger, actively unlocks our DNA-based genome. “We used to have to just infer where these RNAs were acting based on their biological effects,” said Howard Chang, MD, PhD, professor of dermatology. “But now we can identify precisely where on the chromatin they are binding. We’ve found that these sites are focal, numerous and sequence-specific.”

This research greatly improves lab techniques for studying lincRNA, but doesn’t itself identify new functions.

However, the announcement lists several functions already determined, which suggest just how important lincRNAs may be. One type of lincRNA binds to the single X chromosome in male cells. It seems to make transcription more efficient, which is good, since male cells have only one X chromosome instead of the two in female cells.

The telomerase RNA component (TERC) is also a lincRNA. TERC binds to a chromosome’s telomeres so that telomerase can keep them from becoming too short, which is especially important during embryonic development. But interestingly enough, TERC also regulates genes involved in the Wnt pathway – which is also vital during embryonic development and tissue regeneration.

Yet another lincRNA, called HOTAIR, regulates genes that code for polycomb-group proteins. These proteins remodel the chromatin of chromosomes to enable epigenetic silencing of genes. This is known to be important for silencing Hox genes during fruit fly embryonic development.

An obvious theme here is gene regulation in embryonic development. This is a tricky process, since embryonic cells go through a sequence of changes en route to becoming adult cells. Genes have to be turned on and off at the right times so that this process goes smoothly and produces a viable organism, instead of just a blob of cells.

Further reading:

Genomic Maps of Long Noncoding RNA Occupancy Reveal Principles of RNA-Chromatin Interactions

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