Unveiling the Role of N-Terminal Acetylation in Determining the Fate of Cellular Protein Using CRISPR Screens

Unveiling the Role of N-Terminal Acetylation in Determining the Fate of Cellular Protein Using CRISPR Screens

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Researchers at the University of Bergen have elucidated the mechanism  behind N-terminal acetylation, which is one of the most common protein modifications. N-terminal acetylation mark is a key modification that is deposited by N-terminal acetyltransferases (NATs), which protects proteins from degradation and significantly influences cellular processes crucial for longevity and motility.

The role of NATs in dictating protein lifespan, aging and motility

Molecular biologist Sylvia Varland  used the CRISPR-Cas9 screen  to determine the mechanism behind acetyltransferase NatC, a major NAT enzyme. The global CRISPR screen discovered a complex interplay between N-terminal acetylation, ubiquitin ligases, and protein degradation.  Importantly, the research provided evidence that proteins without N-terminal acetylation were marked for degradation by the cellular machinery .Further experiments conducted at the University of Bergen validated that N-terminal acetylation dictated the lifespan of proteins, thereby exerting a profound influence on cellular functions. Surprisingly, NATs and their functionality was found to be conserved, and  fruit flies, serving as an ideal model, showcased parallels in the protein modifications and offered insights into the aging process. Simultaneously, researchers at the University of Aveiro in Portugal explored the consequences of NatC-mediated N-terminal acetylation on longevity and motility using the fruit flies model. The collaborative effort revealed a direct link between this protein modification and decreased longevity and motility with age, providing a holistic view of its impact.

Overall, understanding the mechanism behind NATs mediated N-terminal acetylation not only demystifies protein modifications but also emphasizes the crucial role of NATs in shaping the fate of individual proteins.

Implications for Pharmaceutical and Biotechnology Industries

The most significant takeaway for the pharmaceutical and biotechnology industries lies in understanding the pivotal role of N-terminal acetylation by NATs. This insight opens new avenues for drug development and promising therapeutic strategies, where targeting specific proteins via NATs can be used to  enhance their lifespan. Pharmaceutical and biotechnology companies should closely monitor these findings as they present innovative approaches for novel drug designs and treatments.


The spotlight on N-terminal acetylation by NATs represents a paradigm shift in our understanding of cellular processes. This discovery not only resolves a longstanding puzzle of N-terminal protein acetylation but also lays the groundwork for future advancements.

Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help

BI’s data scientists prioritize studying, understanding, and reporting on the latest developments so we can advise our clients confidently. The generation, storage and analysis of biological data is faster and more accessible than ever before. From pipeline development and software engineering to deploying your existing bioinformatic tools, Bridge Informatics can help you on every step of your research journey.

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Haider M. Hassan, Data Scientist, Bridge Informatics

Haider is one of our premier data scientists. He provides bioinformatic services to clients, including high throughput sequencing, data pre-processing, analysis, and custom pipeline development. Drawing on his rich experience with a variety of high-throughput sequencing technologies, Haider analyzes transcriptional (spatial and single-cell), epigenetic, and genetic landscapes.

Before joining Bridge Informatics, Haider was a Postdoctoral Associate at the London Regional Cancer Centre in Ontario, Canada. During his postdoc, he investigated the epigenetics of late-onset liver cancer using murine and human models. Haider holds a Ph.D. in biochemistry from Western University, where he studied the molecular mechanisms behind oncogenesis. Haider still lives in Ontario and enjoys spending his spare time visiting local parks. If you’re interested in reaching out, please email [email protected] or [email protected]

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