HKUST scientists discover how RNA PoII maintains accurate transcription with super computer

April 02, 2019

The message of life is encoded in our genomic DNA through transcription of messenger RNAs and translation of proteins to perform cellular functions. To ensure accurate transcription - a process that transcribes genomic DNA into messenger RNA by adding nucleotides one by one like letters in the alphabet, an enzyme called RNA polymerase II would synthesize and proofread messenger RNA to remove any mis-incorporated nucleotides that do not match with the DNA template.

While RNA polymerase II was known to be critical in ensuring the accuracy of transcription, it had been a long-standing puzzle as to how this enzyme accomplishes this difficult task. Scientists have always been intrigued to find out the underlying mechanisms, as that could offer insights on how errors could be made during this otherwise highly-accurate transcription process, which may lead to various human diseases.

A research team led by Prof. HUANG Xuhui, Padma Harilela Associate Professor of Science in the Department of Chemistry and Department of Chemical and Biological Engineering at HKUST, recently discovered the mechanism for RNA polymerase II to correct errors in RNA synthesis. When a nucleotide is added by mistake, RNA polymerase II can rewind by moving backwards (called backtracking) and cleave this mis-incorporated nucleotide. The research team found that while specific amino acid residues of RNA polymerase II are critical for backtracking, cleavage of the mis-incorporated nucleotide only requires the RNA itself (i.e. phosphate oxygen of mis-incorporated nucleotide).

"RNA polymerase II is like a molecular machine in the cell. Nature cleverly designs this machine to catalyze two distinct chemical reactions in a single active site without getting mixed-up. While normal RNA synthesis requires specific amino acid residues of RNA polymerase II, we found that the removal of the mismatched nucleotide does not rely on any amino acid residues. This molecular machine seamlessly coordinates these two functions in one active site," said Prof. Huang. "Our discovery offers valuable insights into how transcription may go wrong in ageing and diseased cells, and to what extent transcriptional errors may lead to various human diseases."

"Our work is only possible with the large-scale high-performance computing resources mostly provided by the Shaheen Supercomputer in collaboration with King Abdullah University of Science and Technology (KAUST)", Prof. Huang added. "Our quantum mechanics and molecular dynamics calculations consumed 20 million CPU core hours in total."

The findings were recently published in prestigious scientific journal Nature Catalysis [1].

Prof. Huang's research interest lies in understanding complex biological and chemical processes using computational approaches. The computational work was conducted by Dr. Carmen TSE, a long-time HKUST affiliate who completed her undergraduate, PhD, and post-doctoral training all at HKUST's Department of Chemistry. Other corresponding authors include HKUST's Research Assistant Professor Dr. Peter CHEUNG from Department of Chemistry, Prof. Yingkai ZHANG from New York University, and Prof. WANG Dong from University of California, San Diego whose research group performed experiments to validate the predicted mechanisms from calculations.
-end-
[1] This paper is a follow-up work of Prof. Huang's previous publication to elucidate the mechanisms of RNA polymerase II's backtracking upon mis-incorporation in Nature Communications

Hong Kong University of Science and Technology

Related Quantum Mechanics Articles from Brightsurf:

Theoreticians show which quantum systems are suitable for quantum simulations
A joint research group led by Prof. Jens Eisert of Freie Universit├Ąt Berlin and Helmholtz-Zentrum Berlin (HZB) has shown a way to simulate the quantum physical properties of complex solid state systems.

A new interpretation of quantum mechanics suggests reality does not depend on the measurer
For 100 years scientists have disagreed on how to interpret quantum mechanics.

New evidence for quantum fluctuations near a quantum critical point in a superconductor
A study has found evidence for quantum fluctuations near a quantum critical point in a superconductor.

Simulating quantum 'time travel' disproves butterfly effect in quantum realm
Using a quantum computer to simulate time travel, researchers have demonstrated that, in the quantum realm, there is no 'butterfly effect.' In the research, information--qubits, or quantum bits--'time travel' into the simulated past.

Orbital engineering of quantum confinement in high-Al-content AlGaN quantum well
Recently, professor Kang's group focus on the limitation of quantum confine band offset model, the hole states delocalization in high-Al-content AlGaN quantum well are understood in terms of orbital intercoupling.

A Metal-like Quantum Gas: A pathbreaking platform for quantum simulation
Coherent and ultrafast laser excitation creates an exotic matter phase with spatially overlapping electronic wave-functions under nanometric control in an artificial micro-crystal of ultracold atoms.

Fluid mechanics mystery solved
An environmental engineering professor has solved a decades-old mystery regarding the behavior of fluids, a field of study with widespread medical, industrial and environmental applications.

Quantum leap: Photon discovery is a major step toward at-scale quantum technologies
A team of physicists at the University of Bristol has developed the first integrated photon source with the potential to deliver large-scale quantum photonics.

USTC realizes the first quantum-entangling-measurements-enhanced quantum orienteering
Researchers enhanced the performance of quantum orienteering with entangling measurements via photonic quantum walks.

A convex-optimization-based quantum process tomography method for reconstructing quantum channels
Researchers from SJTU have developed a convex-optimization-based quantum process tomography method for reconstructing quantum channels, and have shown the validity to seawater channels and general channels, enabling a more precise and robust estimation of the elements of the process matrix with less demands on preliminary resources.

Read More: Quantum Mechanics News and Quantum Mechanics Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.