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
LGC Clinical Diagnostics

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
Turnkey Packaging Solution
HLX
Automated Blood Typing System
IH-500 NEXT
New
Automatic Biochemistry Analyzer
Audmax 180 Evolution
New
Chemistry Analyzer
MS100

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

Hematology

view channel
Image: The smartphone technology measures blood hemoglobin levels from a digital photo of the inner eyelid (Photo courtesy of Purdue University)

First-Of-Its-Kind Smartphone Technology Noninvasively Measures Blood Hemoglobin Levels at POC

Blood hemoglobin tests are among the most frequently conducted blood tests, as hemoglobin levels can provide vital insights into various health conditions. However, traditional tests are often underutilized... Read more

Immunology

view channel
Image: Under a microscope, DNA repair is visible as bright green spots (“foci”) in the blue-stained cell DNA. Orange highlights actively growing cancer cells (Photo courtesy of WEHI)

Simple Blood Test Could Detect Drug Resistance in Ovarian Cancer Patients

Every year, hundreds of thousands of women across the world are diagnosed with ovarian and breast cancer. PARP inhibitors (PARPi) therapy has been a major advancement in treating these cancers, particularly... Read more

Microbiology

view channel
Image: HNL Dimer can be a novel and potentially useful clinical tool in antibiotic stewardship in sepsis (Photo courtesy of Shutterstock)

Unique Blood Biomarker Shown to Effectively Monitor Sepsis Treatment

Sepsis remains a growing problem across the world, linked to high rates of mortality and morbidity. Timely and accurate diagnosis, along with effective supportive therapy, is essential in reducing sepsis-related... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.