How invading jumping genes are thwarted

image credit: sciencedaily.com

Since Carnegie Institution's Barbara McClintock received her Nobel Prize on her discovery of jumping genes in 1983, we have learned that almost half of our DNA is made up of jumping genes -- called transposons. Given their ability of jumping around the genome in developing sperm and egg cells, their invasion triggers DNA damage and mutations. This often leads to animal sterility or even death, threatening species survival. The high abundance of jumping genes implies that organisms have survived millions, if not billions, of transposon invasions. However, little is known about where this adaptability comes from.

Now, a team of Carnegie researchers has discovered that, upon jumping gene invasion, reproductive stem cells boost production of non-coding RNA elements (piRNA) that suppress their activity and activates a DNA repair process allowing for normal egg development. The results are published in the November 1, 2018, issue of Developmental Cell.

The researchers studied jumping genes in the fruit fly Drosophila melanogaster -- a classic model to study jumping genes in developing sperm and egg cells. To set up a powerful system studying jumping gene adaptation, the researchers needed a tool to control their activity. It has been known for four decades that environmental temperature influences the severity of sterility in the fruit fly upon jumping gene invasion. At temperatures of 77 degrees F (25 degrees C) offspring have sterile ovaries, while at 64 degrees F (18 degrees C) offspring have fully developed and fertile ovaries.

Small molecules set up security system to defend the genome

via medicalexpress.com

"Thousands of short RNA molecules with diverse genetic sequences serve as security guards to identify and silence attempts to invade the genome, such as DNA inserted by viruses or parasitic elements known as transposons.

These diverse, small RNA molecules, known as Piwi-interacting RNAs (piRNAs) are produced by various animals, from insects and worms to mammals like mice and humans. In a new study published February 2 in the journal Science, researchers from the University of Chicago describe how piRNAs find foreign genetic sequences to silence them. They also show how endogenous or "self" genes that properly belong in the genome identify themselves to avoid this additional scrutiny.

"Nearly every animal has these small RNAs, and they use them as a guide to look for target sequences and silence them," said Heng-Chi Lee, PhD, assistant professor of molecular genetics and cell biology at UChicago and senior author of the new study. "Until now though, it was rather mysterious what their function was, and why there are so many with such diverse genetic sequences."

A database of suspects

RNA acts as a messenger to carry out instructions coded in DNA to produce proteins that perform essential functions in the body. In the new study, Lee and his colleagues studied piRNAs produced by cells in the reproductive system of the nematode worm, C. elegans, a classic model organism studied by scientists to understand basic biological processes.

Piwi-interacting RNAs are a type of small RNAs that associate with what's known as Argonaute machinery in cells that search for target RNA and shut it down. RNA is built with the same chains of nucleotides that mirror sequences of DNA, denoted with the same familiar A, C, G, U lettering. Some small RNAs need to match the target sequence exactly to identify them, like a security guard looking for a specific person. Others small RNAs can flag genes with a partial match, more like looking for a suspect based on a general description..."

Learn more:

https://www.sciencedaily.com/releases/2018/02/180201141508.htm

Sperm RNA may serve as biomarkers of future health

via newscientist.com

"Human sperm may hold the potential to serve as biomarkers of the future health of newborn infants, according to a new study by a Wayne State University School of Medicine research team.

Published in the peer-reviewed journal Systems Biology in Reproductive Medicine, the study, "Sperm RNA elements as markers of health," from the lab of Stephen A. Krawetz, Ph.D., the Charlotte B. Failing Professor of Fetal Therapy and Diagnosis in the Wayne State Department of Obstetrics and Gynecology and Center for Molecular Medicine and Genetics, indicates that RNA found in male sperm not only shows promise as a determinant in successful live birth, it may also tell us more about the health of a child as it matures.

"We explored the opportunity of using sperm RNA elements as a predictor of human health, with applications at the fertility clinic that would go hand-in-hand with the new neonatal intensive care unit genome sequencing to better health outcomes," said Dr. Krawetz, associate director of the C.S. Mott Center for Human Growth and Development. "This leaves the intriguing possibility that, while sperm RNAs delivered to the egg inform the success of live birth, they may also open a pathway to understanding the birth and potential health of each child.

At fertilization, sperm delivers a structurally distinct genome, along with a complement of ribonucleic acids, or RNAs, and proteins to the immature egg cell. To test the hypothesis, sperm RNA elements corresponding to specific genes were characterized as a function of disease association. Dr. Krawetz's team surveyed a total of 278,605 sperm RNA elements called short exon-sized sequences, or SREs, associated with diseases. This functional association of SREs may indicate a future phenotype, providing improved understanding of the father's contribution to the life course of the child as well as the current state of paternal health.

In the future, if those SREs that are mutated or modified can be identified, researchers and physicians may be able to not only forecast disease or conditions, but develop ways to prevent them."

Source:

 https://www.sciencedaily.com/releases/2017/12/171201131633.htm

Long, mysterious strips of RNA affect sperm count

image credit: alnmag.com

"Scientists have found distinctive portions of genetic material -- known as lncRNAs -- that help sperm develop. Male mice lacking a particular lncRNA have low sperm count, suggesting lncRNAs could represent novel infertility drug targets.

"Infertility affects 10 to 15 percent of couples in the United States, with the vast majority of cases due to unknown causes. Approximately 40 percent of these cases are due to male infertility," said senior author Khalil. Khalil and colleagues have been working to understand genetic mechanisms behind male infertility.

His work focuses on long strands of genetic material with elusive functions. The strands, called "long non-coding RNAs" or "lncRNAs" don't seem to encode proteins, but have been implicated in everything from cancer to brain function. Many are located in the testes, suggesting they could also play a role in fertility.

Said Khalil,"LncRNAs have only been discovered several years ago, and thus, provide a great opportunity to explore novel therapeutic targets for a variety of conditions."

How the Study Was Conducted: A team of seven researchers, led by Khalil, collected and measured lncRNA levels during the process of cellular differentiation that leads to sperm production. They found that specific lncRNAs are associated with each stage of sperm development. The researchers also identified lncRNAs and mRNAs that are testes-specific -- that is, not found in other human or mouse tissues. The Case Western Reserve School of Medicine Genomics core facility performed the RNA sequencing..."

Learn more: https://www.sciencedaily.com/releases/2017/08/170824182655.htm

 

Τα microRNA προλαμβάνουν την μετάσταση του καρκίνου του Μαστού

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"Νέα Υόρκη: Ομάδα ερευνητών από το Αντικαρκινικό Κέντρο Memorial Sloan-Kettering της Νέας Υόρκης, εντόπισε αρκετά φυσικά ανθρώπινα microRNA που εμποδίζουν τον καρκίνο του μαστού να δώσει μεταστάσεις στον πνεύμονα και τα οστά, τα δύο βασικά σημεία μετάστασης του καρκίνου του μαστού, σύμφωνα με μελέτη που δημοσιεύεται στο επιστημονικό περιοδικό Nature.

Τα microRNA (μικρό-ριβονουκλεϊκό οξέα) είναι μικρά μονής δέσμης τμήματα του γενετικού υλικού που πιστεύεται ότι ελέγχουν την γονιδιακή έκφραση και μπορεί να προκαλέσουν ή μπλοκάρουν την έκφραση σχετικών με τον καρκίνο γονιδίων.

Σε έρευνα που διενήργησαν οι Αμερικανοί επιστήμονες με επικεφαλής τον Δρ Σοχάι Ταβαζόιε με στόχο τον εντοπισμό ρυθμιστών της καρκινικής μετάστασης, βρήκαν μια ομάδα microRNA για τα οποία η έκφραση έχει χαθεί καθώς τα ανθρώπινα καρκινικά κύτταρα του μαστού αναπτύσσουν την δυνατότητα της μετάστασης.

Σε εργαστηριακά τεστ που πραγματοποίησαν η έκφραση αυτών των microRNA αποκαταστάθηκε, και οδήγησε σε καταστολή της πνευμονικής και οστικής μετάστασης όταν προστέθηκαν κακοήθη καρκινικά κύτταρα του μαστού.

Σε άλλη μελέτη, οι επιστήμονες καλλιέργησαν ανθρώπινους καρκινικούς όγκους του μαστού σε ποντίκια. Η αποκατάσταση ενός microRNA (του miR-126) μείωσε τη συνολική καρκινική ανάπτυξη του όγκου και τον αναδιπλασιασμό και η αποκατάσταση ενός ακόμη microRNA (του miR-335) ανέστειλε την εξάπλωση του καρκίνου..."

Μάθετε περισσότερα:

http://www.konstantinioncenter.org/?p=3010&lang=el

Control of fertility: New player identified

via college.unc.edu

Source: INSERM (Institut national de la santé et de la recherche médicale) | Summary: Individual small RNAs are responsible for controlling the expression of gonadoliberin or GnRH (Gonadotropin-Releasing Hormone), a neurohormone that controls sexual maturation, the appearance of puberty, and fertility in adults, new research shows. The involvement of microRNAs, transcribed from DNA, occurs around birth, and marks a key step in postnatal development.

"Individual small RNAs are responsible for controlling the expression of gonadoliberin or GnRH (Gonadotropin-Releasing Hormone), a neurohormone that controls sexual maturation, the appearance of puberty, and fertility in adults. This has just been demonstrated by the "Development and Plasticity of the Neuroendocrine Brain" team led by Vincent Prévot, Inserm Research Director (Jean-Pierre Aubert Research Centre, Lille). 

The involvement of microRNAs, transcribed from DNA, occurs around birth, and marks a key step in postnatal development. Failure of these microRNAs to act leads to the disruption or even total cessation of GnRH production by the hypothalamic neurons that synthesise it, and hence to infertility. In the most serious cases, sterility may result. Details of this work in mice are published in the 2 May 2016 issue of the journal Nature Neuroscience.

Reproductive function is determined by events that take place in the brain. Gametogenesis (the production of spermatozoa and oocytes) and the secretion of hormones by the ovaries and testes are heavily dependent on the hypophysis, a small gland located below the brain, to which it is connected by a capillary network. The latter is in turn controlled by a glandular "orchestra conductor" located at the base of the brain, the hypothalamus. During postnatal development, activation of a small number of highly specialised neurons (the GnRH neurons) in the hypothalamus leads to the synthesis of a hormone, gonadoliberin or GnRH (Gonadotropin Releasing Hormone), and this process leads to the appearance of puberty..."

Read more here:

https://www.sciencedaily.com/releases/2016/05/160502131405.htm