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Mutations

Mutations

Transfer RNA Synthesis

Transfer RNA Synthesis

One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...

RNA Editing

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...

Mutations

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...

What is Gene Expression?

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...

Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...

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Related Experiment Video

Updated: Jul 8, 2026

An Engineered Split-TET2 Enzyme for Chemical-inducible DNA Hydroxymethylation and Epigenetic Remodeling

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Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.

A G Nackley¹, S A Shabalina, I E Tchivileva

¹Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC 27599, USA.

Science (New York, N.Y.)

|December 23, 2006

Summary

Synonymous variations in the Catechol-O-methyltransferase (COMT) gene influence protein levels and activity, impacting pain sensitivity. Haplotypes, not single SNPs, are crucial for understanding COMT gene function.

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Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry

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Published on: April 21, 2022

Area of Science:

Genetics
Molecular Biology
Neuroscience

Background:

Catechol-O-methyltransferase (COMT) plays a vital role in regulating neurotransmitter levels.
COMT activity is implicated in pain perception, cognitive functions, and mood regulation.
Genetic variations in the COMT gene can affect its enzymatic activity and associated functions.

Purpose of the Study:

To investigate the functional impact of common COMT gene haplotypes on COMT enzymatic activity.
To determine the role of synonymous and nonsynonymous variations within COMT haplotypes.
To explore the relationship between messenger RNA structure and protein expression levels.

Main Methods:

Analysis of three common human COMT gene haplotypes.
Assessment of COMT enzymatic activity differences between haplotypes.
Investigation of messenger RNA local stem-loop structures.
Site-directed mutagenesis to alter RNA structures.

Main Results:

Haplotypes with synonymous changes showed the most significant differences in COMT enzymatic activity.
Reduced translated protein levels were observed in haplotypes with more stable messenger RNA stem-loop structures.
Restoration of protein levels and activity was achieved by disrupting stable RNA structures via mutagenesis.

Conclusions:

Synonymous genetic variations can have a substantial functional impact on protein levels and activity.
Messenger RNA secondary structures play a critical role in regulating COMT protein expression.
Haplotype analysis, rather than single-nucleotide polymorphism analysis, is essential for a comprehensive understanding of COMT gene variation.