Featured Research

from universities, journals, and other organizations

New exception to a decades-old rule about RNA splicing uncovered

Date:
May 17, 2012
Source:
Cold Spring Harbor Laboratory
Summary:
There are always exceptions to a rule, even one that has prevailed for more than three decades, as demonstrated by a new study on RNA splicing, a cellular editing process. The rule-flaunting exception uncovered by the study concerns the way in which a newly produced RNA molecule is cut and pasted at precise locations called splice sites before being translated into protein.

There are always exceptions to a rule, even one that has prevailed for more than three decades, as demonstrated by a Cold Spring Harbor Laboratory (CSHL) study on RNA splicing, a cellular editing process. The rule-flaunting exception uncovered by the study concerns the way in which a newly produced RNA molecule is cut and pasted at precise locations called splice sites before being translated into protein.

Related Articles


"The discovery of this exception could impact current ideas on how missteps in splicing triggered by mutations in the DNA sequence can lead to diseases such as cancer and various genetic disorders," says CSHL Professor Adrian Krainer, Ph.D., who led the research. The study appears in the May 15 issue of Genes & Development.

For a protein to be synthesized by the cell, the instructions encoded within that protein's gene have to be first copied from DNA into RNA. This initial copy, called a pre-messenger RNA, is then edited much like film footage, where the unnecessary bits -- strings of nucleotides called introns -- are snipped out and the remaining bits (called exons) are spliced together. For the cut-and-paste mechanism to work correctly, the cell's splicing machinery initially has to be guided to the correct splice site at the beginning of each intron on the target pre-mRNA by another, smaller RNA called U1.

U1 finds the right spots, or splice sites, by lining up against the target RNA and pairing its own RNA nucleotides or bases (the "letters" of the RNA code, A, U, C, G) with those of the target RNA such that its A nucleotide pairs with the target's U, and its C nucleotide pairs with the target's G nucleotide, or vice-versa. U1's ability to recognize splice sites at the beginning of introns is the strongest when up to 11 bases are paired up with their partners on the target RNA, but in most cases, fewer base pairs are formed.

In 2009, Krainer and postdoctoral researcher Xavier Roca discovered, however, that the U1 RNA could recognize even seemingly imperfect splice sites that did not appear to have the correct matching RNA sequence. Instead of lining up against the first RNA base of the target intron's RNA sequence, U1 can sometimes slide down the sequence to the next base if this shift will allow more of the U1 bases to pair up with the target's bases and thereby produce a stronger match.

Krainer and Roca have now found a second, and much more prevalent, alternative option. Instead of shifting away from the first base, they show using a combination of experimental and computational approaches that one or more bases on either U1 or its target can "bulge out" -- or pull away from the lineup -- if this allows the surrounding nucleotides to produce a stronger match between U1 and the target.

Based on studying splice sites in about 6,500 human genes, they estimate that up to 5% of all splice sites, present in 40% of human genes use this "bulge" mechanism to be recognized. Interestingly, some of these atypically recognized sites occur within genes which when mutated lead to disease, and others are sites where alternative splicing -- allowing a single pre-mRNA to give rise to different proteins -- can occur.

"This study expands what we thought were the rules for splice site recognition by U1," said Michael Bender, Ph.D., who oversees RNA processing grants at the National Institutes of Health's National Institute of General Medical Sciences (NIGMS), which partially supported the study. "By extending our understanding of how the splicing process works, the findings may help us pinpoint the splicing defects that underlie certain diseases and develop new therapeutics to treat them."

The work was supported by a National Institutes of Health grant (GM42699).


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. X. Roca, M. Akerman, H. Gaus, A. Berdeja, C. F. Bennett, A. R. Krainer. Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes & Development, 2012; 26 (10): 1098 DOI: 10.1101/gad.190173.112

Cite This Page:

Cold Spring Harbor Laboratory. "New exception to a decades-old rule about RNA splicing uncovered." ScienceDaily. ScienceDaily, 17 May 2012. <www.sciencedaily.com/releases/2012/05/120517193139.htm>.
Cold Spring Harbor Laboratory. (2012, May 17). New exception to a decades-old rule about RNA splicing uncovered. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2012/05/120517193139.htm
Cold Spring Harbor Laboratory. "New exception to a decades-old rule about RNA splicing uncovered." ScienceDaily. www.sciencedaily.com/releases/2012/05/120517193139.htm (accessed October 24, 2014).

Share This



More Plants & Animals News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. 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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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