Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer-associated long non-coding RNA regulates pre-mRNA splicing

24.09.2010
Researchers report this month that MALAT1, a long non-coding RNA that is implicated in certain cancers, regulates pre-mRNA splicing – a critical step in the earliest stage of protein production. Their study appears in the journal Molecular Cell.

Nearly 5 percent of the human genome codes for proteins, and scientists are only beginning to understand the role of the rest of the "non-coding" genome. Among the least studied non-coding genes – which are transcribed from DNA to RNA but generally are not translated into proteins – are the long non-coding RNAs (lncRNAs).

Before the human genome was fully sequenced, it was a "protein-centric world," said University of Illinois cell and developmental biology professor Kannanganattu Prasanth, who led the study. With the sequencing of the genome it became clear, however, that a majority of genes code for RNAs that are not translated into proteins.

In recent years, research on non-coding RNAs has blossomed, but most studies have focused only on small non-coding RNAs, which play critical roles in several aspects of cellular function. There have been comparatively fewer studies on lncRNAs, Prasanth said. As a result, researchers are only beginning to understand the functions of a few lncRNAs.

Prasanth's laboratory focuses on understanding the role of lncRNAs, such as MALAT1, which normally are distributed in the nucleus of mammalian cells.

Preliminary studies suggest that lncRNAs carry out vital regulatory functions in cells. When those functions go awry, Prasanth said, serious consequences can result. Abnormal expression of the MALAT1 gene, for example, is implicated in many cancers, including breast, lung and liver cancers, "so the scientific world was interested in what this RNA could be doing in normal cells, and how changes in its expression correlate with cancer," he said.

Prasanth was also the co-first-author of another study, recently published in The EMBO Journal, that found that MALAT1 plays a role in recruiting important proteins, called pre-mRNA splicing factors, to the site of gene transcription in the nucleus.

Pre-mRNA splicing involves cutting out unneeded sequences and piecing the mRNAs together before they are exported from the nucleus and translated into proteins.

"That study gave us the clue that MALAT1 is an important gene that might be involved in pre-mRNA metabolism," Prasanth said.

In the new study, Prasanth and his colleagues tested the hypothesis that MALAT1 interacts with and modulates the behavior of a group of pre-mRNA splicing factors known as the SR-family splicing factors.

The researchers found that the MALAT1 sequence contains multiple regions that can bind SR-splicing proteins. Further experiments showed that MALAT1 does indeed bind to several members of the SR-proteins the team analyzed.

Furthermore, depleting cells of MALAT1 or over-expressing the splicing factors to which it can bind led to the same alteration in the splicing of a large number of pre-mRNAs in the cells, suggesting that MALAT1 latches onto the splicing factors and regulates their access to new transcripts.

"All of the data strongly suggest that MALAT1 is acting as a regulator of splicing by modulating the levels of the splicing factors in the cell," Prasanth said.

This study verifies that MALAT1 plays a key role in pre-mRNA processing, with broad implications for human health, Prasanth said.

"Numerous studies have shown that aberrant splicing of pre-mRNA is a major issue associated with several diseases, including cancer," he said. "Some of the factors we know interact with MALAT1 have been shown to be oncogenes. If you over-express these genes you can make a cell cancerous."

"Similarly, some of the genes whose pre-mRNA splicing is controlled by MALAT1 are members of the cancer 'signature genes,' " Prasanth said. "This means that their abnormal expression is directly correlated with several cancers."

Post-doctoral researcher Vidisha Tripathi led this work, with assistance from undergraduate student David Song. Supriya Prasanth, a professor of cell and developmental biology at Illinois, and her graduate student, Zhen Shen, also contributed to the study. The research team also included scientists from the University of Toronto; ISIS Pharmaceuticals, Carlsbad, Calif.; and Wright State University, Dayton, Ohio.

Editor's notes: To reach Kannanganattu Prasanth, e-mail
kumarp@illinois.edu

Diana Yates | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>