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Related Experiment Video

Updated: Jul 19, 2026

Decomposing the Variance in Reading Comprehension to Reveal the Unique and Common Effects of Language and Decoding

Decomposing the Variance in Reading Comprehension to Reveal the Unique and Common Effects of Language and Decoding

Published on: October 11, 2018

Transcript-assisted transcriptional proofreading.

Nikolay Zenkin¹, Yulia Yuzenkova, Konstantin Severinov

¹Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA. nicserzen@mail.ru

Science (New York, N.Y.)

|July 29, 2006

Summary

DNA-dependent RNA polymerases (RNAPs) ensure accurate gene expression through a proofreading mechanism. A misincorporated nucleotide in the nascent RNA transcript triggers hydrolysis, correcting errors during transcription elongation for stable heredity.

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Area of Science:

Molecular Biology
Genetics
Biochemistry

Background:

Stable heredity and accurate gene expression depend on the fidelity of nucleic acid synthesis.
The precise mechanisms governing transcription fidelity by DNA-dependent RNA polymerases (RNAPs) remain incompletely understood.
Understanding RNAP fidelity is crucial for comprehending genetic stability and preventing disease.

Purpose of the Study:

To elucidate the molecular mechanism by which DNA-dependent RNA polymerases (RNAPs) ensure transcription fidelity.
To investigate the role of the nascent transcript's 3' end in proofreading during transcription elongation.

Main Methods:

Investigated the role of the 3'-terminal nucleotide of the nascent RNA transcript in stimulating hydrolytic activity.
Utilized biochemical assays to monitor phosphodiester bond hydrolysis within the RNAP active center.
Compared the hydrolytic stimulation caused by correctly versus misincorporated nucleotides.

Main Results:

The 3' end-proximal nucleotide of the nascent transcript actively participates in the RNAP active center.
This nucleotide stimulates the hydrolysis of the penultimate phosphodiester bond, particularly when misincorporated.
The hydrolytic reaction effectively proofreads and corrects the majority of misincorporation events during elongation.

Conclusions:

DNA-dependent RNA polymerases possess an intrinsic proofreading mechanism involving transcript hydrolysis.
Misincorporated nucleotides trigger enhanced hydrolysis, serving as a key factor in maintaining transcription fidelity.
This mechanism is vital for ensuring genetic stability and accurate gene expression.