Featured Research

from universities, journals, and other organizations

Genomic 'dark matter' of embryonic lungs controls proper development of airways

Date:
June 18, 2014
Source:
Perelman School of Medicine at the University of Pennsylvania
Summary:
Hundreds of long non-coding RNAs expressed in developing and adult lungs have been identified by researchers. Many of these non-protein-coding RNAs in the lung regulate gene expression by opening and closing the DNA scaffolding on neighboring genes.

The developing lung has similar expression patterns (red) of Nkx2-1 (bottom) and the novel long non-coding RNA NANCI (top), which promotes Nkx2-1 expression. Cell nuclei are stained blue.
Credit: Michael Herriges, Perelman School of Medicine, University of Pennsylvania

It's a long way from DNA to RNA to protein, and only about two percent of a person's genome is eventually converted into proteins. In contrast, a much higher percentage of the genome is transcribed into RNA. What these non-protein-coding RNAs do is still relatively unknown. However, given their vast numbers in the human genome, researchers believe that they likely play important roles in normal human development and response to disease.

Related Articles


Large-scale sequencing has allowed investigators to identify thousands of non-coding RNAs. Small non-coding RNAs, including microRNAs, are known to be important players in regulating gene expression in many contexts, including tissue development. On the other hand, the function of long non-coding RNAs (lncRNAs) is less well understood.

Research led by Ed Morrisey, PhD, professor of Medicine and Cell and Developmental Biology in the Perelman School of Medicine, University of Pennsylvania and scientific director of the Penn Institute for Regenerative Medicine, has identified hundreds of these lncRNAs, sometimes called the "genomic dark matter," that are expressed in developing and adult lungs. Their findings, described in and featured on the cover of the current issue of Genes and Development, reveal that many of these lncRNAs in the lung regulate gene expression by opening and closing the DNA scaffolding on neighboring genes.

The team identified 363 long non-coding RNAs in the lung of the embryonic and adult mouse. They show that these lncRNAs are often located near transcription factors in the genome of lung cell lineages. "We have defined a new association of long non-coding RNAs with proteins called transcription factors that bind to specific DNA sequences and control cell identity and function," Morrisey says. "This association is important for lung development in mouse embryos, and at least for one of these long non-coding RNAs, important for human lung function."

Critical Pathways for Development, Disease

The team identified a lncRNA, called NANCI, that regulates the critical transcription factor Nkx2.1. This factor is the first lung molecular marker during mouse and human development and is essential for lungs to mature properly in an embryo.

NANCI appears to act upstream of Nkx2.1, but down-stream of Wnt signaling, a critical pathway for specifying cell type later in lung tissue development. Knockdown of NANCI expression during lung development leads to decreased Nkx2.1 expression and mimics the defects due to loss of a single copy of the Nkx2.1 gene, including decreased expression of surfactant proteins. These proteins aid in marking bacteria invading the lung for destruction by the immune system.

Importantly, patients with mutations in a single copy of NKX2.1 often have Brain-Lung-Thyroid Syndrome, which is characterized by respiratory distress after birth and accompanied by decreased surfactant protein expression. "There is also a report of a patient with a deletion in NANCI but not NKX2.1 who has Brain-Lung-Thyroid Syndrome, suggesting that mutations in NANCI and other lncRNAs can underlie human diseases," explains Morrisey.

In addition to NANCI, the team identified another lncRNA, which they named LL34, that regulates retinoic acid signaling, another important pathway for early lung development. LL34 is highly expressed in the early developing foregut, a region of the embryo that generates multiple tissue types, including lung, thyroid, and liver. Knockdown of LL34 expression leads to decreased retinoic acid signaling, suggesting that this lncRNA may play an early role in the development of the lung, as well as other tissues controlled by this pathway.

While other lncRNAs expressed in the lung, such as MALAT1, may primarily play a role in cancer progression, the data generated by the Morrisey lab provides unique insight into lncRNAs that regulate lung development. "We are hopeful that these new data provide the foundation for a better understanding of how the non-coding transcriptome regulates tissue development and also maintenance of adult tissues," says Morrisey.

Future work will be directed towards understanding how these lncRNAs control lung development, as well as adult lung regeneration using both mouse and human model systems.


Story Source:

The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. J. Herriges, D. T. Swarr, M. P. Morley, K. S. Rathi, T. Peng, K. M. Stewart, E. E. Morrisey. Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development. Genes & Development, 2014; 28 (12): 1363 DOI: 10.1101/gad.238782.114

Cite This Page:

Perelman School of Medicine at the University of Pennsylvania. "Genomic 'dark matter' of embryonic lungs controls proper development of airways." ScienceDaily. ScienceDaily, 18 June 2014. <www.sciencedaily.com/releases/2014/06/140618184549.htm>.
Perelman School of Medicine at the University of Pennsylvania. (2014, June 18). Genomic 'dark matter' of embryonic lungs controls proper development of airways. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2014/06/140618184549.htm
Perelman School of Medicine at the University of Pennsylvania. "Genomic 'dark matter' of embryonic lungs controls proper development of airways." ScienceDaily. www.sciencedaily.com/releases/2014/06/140618184549.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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


Health & Medicine

Mind & Brain

Living & Well

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