Any expectant mother would want her baby's organs to develop properly in the womb but what she doesn’t know is that a child's internal organs continue to develop for months and years after birth. Various cellular changes take place in this critical period. These changes transform the organization and function of most tissues. But until now the exact mechanisms underlying postnatal organ maturation were still a mystery. 
Recently researchers reported that liver cells utilize a mechanism called "alternative splicing," which alters how genes are translated into the proteins that guide this critical period of development.
Biochemistry Professor Auinash Kalsotra from The University of Illinois, who has led this study, said that this mechanism is totally different from simply turning gene expression on or off.
"Turning gene expression on or off leads to a quantitative change in gene expression - you make more or less of a particular RNA. Alternative splicing, however, provides means to produce a qualitative change. You are making the same amounts of RNA but of different kinds."
Alternative splicing is a lot like building with LEGOs, where bits and pieces of DNA (called exons) can be pieced together or have parts removed to produce different assortments of proteins.
Kalsotra said that the diversity of RNAs and proteins generated in this way allows the liver to acquire new functions tailored for the adult needs.
Using a powerful technology called next-generation RNA sequencing, the researchers simultaneously looked at thousands of genes, pinpointing the ones that undergo regulated changes in alternative splicing as the liver develops.
The findings also identified an RNA binding Protein, ESRP2, which controls this developmental program in the liver.
"It turns out that ESRP2 is absent in the fetal liver and is only turned on after birth to activate splicing of genes that are particularly important for liver growth and functionality," Kalsotra said.
Working in cell culture, the researchers spurred liver cells to express the ESRP2 Protein, and observed that the cells began to display adult-like characteristics.
"We were amazed to see how clean the results were," Kalsotra said. "In the absence of ESRP2, the adult liver remains immature. This tells us how important this RNA binding Protein is for optimizing adult functions."
This is the first study to provide a direct link between splicing regulation and liver maturation, he said.
"We are excited to investigate this link further and determine the exact function of these splicing switches in postnatal liver development," said Kalsotra, who also is an affiliate of the Carl R. Woese Institute for Genomic Biology at Illinois.
Amruta Bhate, a graduate student in the Kalsotra lab, and Darren Parker, an Illinois Biochemistry undergraduate student, spearheaded this work. The research team also included Waqar Arif, Edrees H. Rashan, Sandip Chorghade, Anthony Chau and Sayeepriyadarshini Anakk, from the University of Illinois, Urbana-Champaign; Thomas W. Bebee and Russ P. Carstens, from University of Pennsylvania; and Jaegyoon Ahn, Jae-Hyung Lee, and Xinshu Xiao from University of California, Los Angeles. Parker and Chau are currently graduate students at Massachusetts Institute of Technology and University of California, Los Angeles respectively.
This study was funded by The National Institutes of Health, March of Dimes, and Roy J. Carver Charitable Trust.
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