Navigation Links
CSHL team solves a protein complex's molecular structure to explain its role in gene silencing

Cold Spring Harbor, N.Y. A cell's genome maintains its integrity by organizing some of its regions into a super-compressed form of DNA called heterochromatin. In the comparatively simple organism fission yeast, a cellular phenomenon known as RNA interference (RNAi) plays an essential role in assembling heterochromatin, which keeps the compressed DNA in an inactive or "silent" state. Central to this process is a large protein complex that physically anchors various molecules involved in heterochromatin assembly to the chromatin fibers.

By probing the three dimensional structure of this protein complex, called RNA-Induced Initiation of Transcriptional gene Silencing (RITS), scientists from Cold Spring Harbor Laboratory (CSHL) and their collaborators at St. Jude's Research Hospital have discovered new details of how its various parts or "domains" contribute to heterochromatin assembly and gene silencing. The study appears in Nature Structural & Molecular Biology on Nov. 13.

"Heterochromatin formation relies on the RNAi pathway, and the RITS complex is the central, linking player that makes this possible," explains CSHL Professor and HHMI Investigator Leemor Joshua-Tor, Ph.D. The RITS complex is composed of three proteins, including Ago1, a key component of the cell's RNAi machinery. When Ago1 binds to small interfering RNAs (siRNAs) that originate from a specific genomic region, it helps shut down the activity of that genomic region.

The second member of the RITS complex is a protein called Chp1, which acts like a molecular Velcro that specifically attaches to those areas of chromatin that have been chemically marked by methyl groups. The third RITS component is a largely flexible protein called Tas3 that bridges Chp1 and Ago1.

"Our strategy to understand how these various modules of the RITS complex work has been to find out what these structures look like and how they connect to each other and to chromatin," says Joshua-Tor. For the last few years, her team has explored these questions in fission yeast.

In the current study, the combined use of X-ray crystallography and biochemisty by Research Investigator Thomas Schalch, Ph.D., has yielded a much better picture and revealed further details of how Chp1 interacts with the Tas3 protein. These experiments have also identified a previously unknown substructure at the very end of Chp1.

A clue about what role this structure, called the PIN domain, might play in heterochromatin assembly came from scouring a protein database. The team found that other proteins that had similar structural features were associated with telomeres, the cap-like structures at the end of chromosomes. In fission yeast, telomeres are one of the locations where heterochromatin is found, another being the centromere -- the dense knob-like structure at the center of a chromosome.

The team found that deleting the PIN domain from Chp1 prevented heterochromatin formation at the telomeres but didn't affect formation at the centromere. "This suggests different functions of RITS proteins at centromeres vs telomeres," says Joshua-Tor. "RITS might be exerting its effect at centromeres through Ago1 and the RNAi machinery, but might enforcing its function at the telomeres through Chp1 and its PIN domain." The team is now turning its focus to understanding how these various functions are regulated.

Contact: Hema Bashyam
Cold Spring Harbor Laboratory

Related biology news :

1. Scripps research team solves structure of beneficial virus
2. Genetic sleuth solves glaucoma mystery
3. Brown biologist solves mystery of tropical grasses origin
4. A collaboration solves the herpes virus protein structure providing new drug therapy directions
5. Mystery dissolves with calcium pump discovery
6. Of mice and men: UNC-led team solves mouse genome dilemma
7. Team solves decades-old molecular mystery linked to blood clotting
8. DNA solves identities of Australian melons and loofah
9. Robot biologist solves complex problem from scratch
10. Photonic crystal biosensors detect protein-DNA interactions
11. Penn biophysicists create new model for protein-cholesterol interactions in brain and muscle tissue
Post Your Comments:
(Date:11/9/2015)... JOSE, Calif. , Nov. 9, 2015  Synaptics ... human interface solutions, today announced broader entry into the ... vehicle-specific solutions that match the pace of consumer electronics ... and biometric sensors are ideal for the automotive industry ... vehicle. Europe , ...
(Date:10/29/2015)... Oct. 29, 2015   MedNet Solutions , an ... spectrum of clinical research, is pleased to announce that ... Association (MHTA) as one of only three finalists for ... – Small and Growing" category. The Tekne Awards honor ... shown superior technology innovation and leadership. ...
(Date:10/29/2015)... ANN ARBOR, Mich. , Oct. 29, 2015 ... with Eurofins Genomics for U.S. distribution of its ... DNA-seq kit and Rubicon,s new ThruPLEX Plasma-seq ... DNA to enable the preparation of NGS libraries ... in plasma for diagnostic and prognostic applications in ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... ... December 01, 2015 , ... The American ... Dr. J. Kyle Mathews will join fellow surgeons in the shared ... hysterectomy. , An experienced urogynecologist, founder of Plano Urogynecology Associates and Fellow ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... join physicians, aesthetic practitioners and aesthetics professionals from Central America and abroad for ... held in Panama City, Panama Feb. 17-19, 2016. Testart will present and discuss ...
(Date:11/30/2015)... ... ... Group announced the opening of a new core patient care hub with the opening ... facilities are part of GSCG’s expansion efforts in Latin America. , Both the Arica ... patients from around the world. , The clinics will be headed by Victor Perez, M.D. ...
(Date:11/30/2015)... 2015 Partnership includes an MPP ... for the u niversity , s ... treatment s cale - up through ... Africa , where licensees based anywhere in the world will have ... --> Africa , where licensees based anywhere in the world ...
Breaking Biology Technology: