Scientists uncover mechanism that propels liver development after birth

Scientists uncover mechanism that propels liver development after birth
Alternative splicing generates mRNA diversity to support liver development. Credit: Model/Adit Kalsotra

Any expectant mother will tell you that she wants her baby's organs to develop properly in the womb.

What she may not realize, however, is that a child's internal organs continue to develop for months and years after birth. This critical period is full of cellular changes that transform the organization and function of most tissues. But the exact mechanisms underlying postnatal organ maturation are still a mystery.

Now researchers report that cells utilize a mechanism called "," which alters how genes are translated into the proteins that guide this critical period of development.

"This mechanism is different from simply turning gene expression on or of," said University of Illinois Biochemistry Professor Auinash Kalsotra, who led the study.

"Turning gene expression on or off leads to a quantitative change in - 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.

"The diversity of RNAs and proteins generated in this way allows the liver to acquire new functions tailored for the adult needs," Kalsotra said.

Scientists uncover mechanism that propels liver development after birth
Alternative splicing generates mRNA diversity to support liver development. Credit: Model/Adit Kalstotra

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, which appear in the journal Nature Communications, 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 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.


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More information: Amruta Bhate et al. ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation, Nature Communications (2015). DOI: 10.1038/NCOMMS9768
Journal information: Nature Communications

Citation: Scientists uncover mechanism that propels liver development after birth (2015, November 4) retrieved 17 October 2019 from https://medicalxpress.com/news/2015-11-scientists-uncover-mechanism-propels-liver.html
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JVK
Nov 04, 2015
Excerpt: ..."alternative splicing," which alters how genes are translated into the proteins that guide this critical period of development.

See also: From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

Excerpt: "Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans..."

Our detailed model of how conserved molecular mechanisms link RNA-mediated events from sex differences in cell types to all differences in cell types in all individuals of all living genera was extended from the mouse model to human via metabolic networks from the liver to genetic networks in "Nutrient-dependent/pheromone-controlled adaptive evolution: a model" http://www.ncbi.n...24693353

JVK
Nov 04, 2015
Excerpt: "...the first study to provide a direct link between splicing regulation and liver maturation, he said."

The mouse model was linked to human physiology and behavior in my 2013 review.

http://www.ncbi.n...24693353 Excerpt: "Two additional recent reports link substitution of the amino acid alanine for the amino acid valine (Grossman et al., 2013) to nutrient-dependent pheromone-controlled adaptive evolution. The alanine substitution for valine does not appear to be under any selection pressure in mice. The cause-and-effect relationship was established in mice by comparing the effects of the alanine, which is under selection pressure in humans, via its substitution for valine in mice (Kamberov et al., 2013)."

These two studies also linked another single amino acid substitution to differences in morphological and behavioral phenotypes in all vertebrates via substitution of the achiral amino acid glycine in position 6 of the GnRH decapeptide.

JVK
Nov 04, 2015
Re: "... achiral amino acid glycine in position 6 of the GnRH decapeptide."

See: "Feedback loops link odor and pheromone signaling with reproduction" http://www.ncbi.n...16290036

Excerpt: "Indications that GnRH peptide plays an important role in the control of sexual behaviors suggest that pheromone effects on these behaviors might also involve GnRH neurons." p 683.

That fact was established in the context of links from atoms to ecosystems in all living genera that begin with nutrient-dependent changes in base pairs and end with the pheromone-controlled physiology of reproduction in species from microbes to man. See: Structural diversity of supercoiled DNA http://dx.doi.org...omms9440

RNA-mediated gene duplication and RNA-mediated amino acid substitutions are the links from the epigenetic landscape to the physical landscape of DNA.

Virus-driven mutations perturb the RNA-mediated events that protect organized genomes from entropy.

JVK
Nov 04, 2015
ISOFORM http://www.merria.../isoform
: any of two or more functionally similar proteins that have a similar but not identical amino acid sequence and are either encoded by different genes or by RNA transcripts from the same gene which have had different exons removed

Use of the term "isoform" in the context of fixed amino acid substitutions that differentiate all cell types is a trick that helps pseudoscientists continue to claim mutations can be linked from natural selection to the evolution of increasing complexity, despite the fact that increasing organismal complexity requires the nutrient-dependent de novo creation of genes.

Nutrients are the anti-entropic force that prevents genomic entropy. Biologically uninformed science idiots have claimed that natural selection is the anti-entropic force that links mutations to evolution.

New evidence for quantum Darwinism found in quantum dots http://phys.org/news192693808.

Nov 04, 2015
Once again JVK references a study he doesn't understand.

"ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation"
http://www.nature...768.html

Nutrients and pheromones are never mentioned. Atoms to ecosystems is never mentioned.
Fertilization isn't mentioned nor adult sexual behavior.

The authors certainly weren't going to cite Kohl's debunked model:
http://www.ncbi.n...4049134/

JVK
Nov 04, 2015
Liver maturation is nutrient-dependent and it links metabolic networks to genetic networks via RNA-mediated gene duplication and RNA-mediated amino acid substitutions that are the basis for everything known to serious scientists about how atoms and ecosystems are linked from nutritional epigenetics to pharmacogenomics.

Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing http://www.medsca...24253661

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