We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Researchers Identify Proteins Required for X Chromosome Silencing by the Long Noncoding RNA Xist

By LabMedica International staff writers
Posted on 13 May 2015
Print article
Image: Artist\'s illustration of an X-chromosome. Investigators showed how the lncRNA Xist orchestrates the silencing of all genes across the entire chromosome (Photo courtesy of the California Institute of Technology).
Image: Artist\'s illustration of an X-chromosome. Investigators showed how the lncRNA Xist orchestrates the silencing of all genes across the entire chromosome (Photo courtesy of the California Institute of Technology).
A recent paper identified a group of proteins that interact directly with the long noncoding RNA (lncRNA) Xist, which is required for transcriptional silencing of one X chromosome during development in female mammals.

Long non-coding RNAs (long ncRNAs, lncRNA) are non-protein coding transcripts longer than 200 nucleotides. This somewhat arbitrary limit distinguishes lncRNAs from small regulatory RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. LncRNAs have been found to be involved in numerous biological roles including imprinting, epigenetic gene regulation, cell cycle and apoptosis, and metastasis and prognosis in solid tumors. Most lncRNAs are expressed only in a few cells rather than whole tissues, or they are expressed at very low levels, making them difficult to study.

The lncRNA Xist is essential to the process of silencing one copy of the X chromosome in female embryos. Having two copies of the X chromosome is an abnormality that leads to death early of the embryo during development.

Investigators at the California Institute of Technology (Pasadena, CA, USA) developed a technique to identify those proteins that naturally interact with Xist in the cell. They combined RNA antisense purification with mass spectrometry (RAP-MS). The investigators used the antisense purification technique to extract and purify Xist lncRNA molecules, as well as the proteins that directly interact with Xist, from mouse embryonic stem cells. Then, they employed quantitative mass spectrometry to identify those interacting proteins.

They reported in the April 27, 2015, online edition of the journal Nature that 10 proteins were specifically associated with Xist. Three of these proteins—SAF-A (Scaffold attachment factor-A), LBR (Lamin B Receptor), and SHARP (SMRT and HDAC associated repressor protein)—were required for Xist-mediated transcriptional silencing. Further analysis revealed that the direct interaction of Xist and SHARP triggered a series of steps that led to the exclusion of RNA polymerase II from the cell's DNA, thus preventing transcription and gene expression.

Senior author Dr. Mitchell Guttman, assistant professor of biology and biological engineering at the California Institute of Technology, said, "To start to make sense of what makes lncRNAs special and how they can control all of these different cellular processes, we need to be able to understand the mechanism of how any lncRNA gene can work. Because Xist is such an important molecule and because so much is known about what it does, it seemed like a great system to try to dissect the mechanisms of how it and other lncRNAs work. We are starting to pick apart how lncRNAs work. We now know, for example, how Xist localizes to sites on X, how it silences transcription, and how it can change DNA structure. One of the things that is really exciting for me is that we can potentially leverage the principles used by lncRNAs, move them around in the genome, and use them as therapeutic agents to target specific defective pathways in disease."

Related Links:

California Institute of Technology


Gold Member
Flocked Fiber Swabs
Puritan® Patented HydraFlock®
Antipsychotic TDM Assays
Saladax Antipsychotic Assays
New
Thyroid ELISA Kit
AESKULISA a-TPO
New
Cortisol Rapid Test
Finecare Cortisol Rapid Quantitative Test

Print article

Channels

Clinical Chemistry

view channel
Image: The new saliva-based test for heart failure measures two biomarkers in about 15 minutes (Photo courtesy of Trey Pittman)

POC Saliva Testing Device Predicts Heart Failure in 15 Minutes

Heart failure is a serious condition where the heart muscle is unable to pump sufficient oxygen-rich blood throughout the body. It ranks as a major cause of death globally and is particularly fatal for... Read more

Molecular Diagnostics

view channel
Image: The bowel cancer breakthrough could result in better treatment outcomes (Photo courtesy of 123RF)

New RNA Molecules Can Help Predict Bowel Cancer Return Recurrence

Colorectal cancer accounts for 10% of all cancer-related deaths worldwide and was ranked as the second most common cause of cancer death in the United States in 2022. Currently, clinicians face diagnostic... Read more

Hematology

view channel
Image: QScout CBC will give a complete blood count in 2 minutes from fingerstick or venous blood (Photo courtesy of Ad Astra Diagnostics)

Next Gen CBC and Sepsis Diagnostic System Targets Faster, Earlier, Easier Results

Every hour is critical in protecting patients from infections, yet there are currently limited tools to assist in early diagnosis before patients reach a hospital. The complete blood count (CBC) is a common... Read more

Microbiology

view channel
Image: The InfectoSynovia test has the potential to revolutionize the diagnosis of periprosthetic joint infection (Photo courtesy of 123RF)

High-Accuracy Bedside Test to Diagnose Periprosthetic Joint Infection in Five Minutes

Periprosthetic joint infection (PJI) represents a significant global issue that is worsening as the number of joint replacements increases due to aging populations. In the United States alone, the anticipated... Read more

Pathology

view channel
Image

AI-Based Method Shows Promise for Pathological Diagnosis of Hereditary Kidney Diseases

Alport syndrome is a hereditary kidney disorder characterized by kidney dysfunction, sensorineural hearing loss, and ocular abnormalities. Early in the disease, patients experience hematuria, which is... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.