Featured Research

from universities, journals, and other organizations

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

Date:
September 27, 2010
Source:
University of Illinois at Urbana-Champaign
Summary:
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.

Cell and developmental biology professor Kannanganattu Prasanth (left), post-doctoral researcher Vidisha Tripathi (seated), undergraduate research assistant David Song and their colleagues found that a long non-coding RNA, MALAT1, plays a key role in pre-mRNA processing. Aberrant regulation of the MALAT1 gene is associated with several cancers, as are some of the splicing factors it regulates. Similarly, some of the genes whose pre-mRNA splicing is regulated by MALAT1 are cancer "signature genes."
Credit: L. Brian Stauffer, U. of I. News Bureau.

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.


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Journal Reference:

  1. Vidisha Tripathi, Jonathan D. Ellis, Zhen Shen, David Y. Song, Qun Pan, Andrew T. Watt, Susan M. Freier, C. Frank Bennett, Alok Sharma, Paula A. Bubulya. The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor Phosphorylation. Molecular Cell, 2010; DOI: 10.1016/j.molcel.2010.08.011

Cite This Page:

University of Illinois at Urbana-Champaign. "Cancer-associated long non-coding RNA regulates pre-mRNA splicing." ScienceDaily. ScienceDaily, 27 September 2010. <www.sciencedaily.com/releases/2010/09/100923162412.htm>.
University of Illinois at Urbana-Champaign. (2010, September 27). Cancer-associated long non-coding RNA regulates pre-mRNA splicing. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2010/09/100923162412.htm
University of Illinois at Urbana-Champaign. "Cancer-associated long non-coding RNA regulates pre-mRNA splicing." ScienceDaily. www.sciencedaily.com/releases/2010/09/100923162412.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Reasons Why Teen Birth Rates Are At An All-Time Low

Reasons Why Teen Birth Rates Are At An All-Time Low

Newsy (Aug. 20, 2014) A CDC report says birth rates among teenagers have been declining for decades, reaching a new low in 2013. We look at several popular explanations. Video provided by Newsy
Powered by NewsLook.com
Common Antibiotic Could Lead To Heart-Related Death

Common Antibiotic Could Lead To Heart-Related Death

Newsy (Aug. 20, 2014) Danish researchers discovered patients taking clarithromycin have an increased risk of dying from a heart-related issue. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins