RNA interference and cellular imbalances affect disease and ageing

Ageing is a complex process shaped by genetic, environmental and cellular processes. RNAi is increasingly recognized for its role in regulating ageing and now attention is turning to RNAi processes in the cell nucleus, which are thought to play a special role.

All cells in the body contain identical DNA and therefore the same genetic instructions for making the proteins the body needs. Although cells have identical genetic information, they are in fact very different. For example, there are muscle cells, brain cells and skin cells. This diversity is the result of a process called gene regulation, which affects how the genetic instructions present in all cells are expressed. Exactly how genes are regulated depends on several coordinated mechanisms, including RNA interference (RNAi), which controls which genes are active. When this process does not work properly, it can lead to diseases. 

RNAi works through a protein called Argonaute (AGO) and small RNA molecules called microRNAs (miRNAs) that attach to messenger RNAs (mRNAs) and cause them to be degraded. Although much is known about how RNAi works in the main part of the cell, the cytoplasm, new findings show that RNAi also occurs in the nucleus.

AGO has been shown to play an important role in the cell nucleus during early development, but is normally kept outside the nucleus in healthy adult cells. However, in viral infections, cancer and during ageing, AGO can end up in the nucleus, which can worsen the disease/condition. If AGO could be blocked in the nucleus, it might be a new way to treat these conditions.

Associate Professor Aishe Sarshad, Department of Biomedicine at the University of Gothenburg, is investigating the link between RNAi processes in the cell nucleus and aging. The research team will study cells from progeria patients, characterized by accelerated aging, and patient cells with systemic sclerosis, showing a more normal aging process, as well as from young healthy and young people. Localizing AGO proteins in the cell and restoring their function in the cytoplasm may be a key to a novel, innovative and promising strategy to address disease progression and the molecular effects of ageing.

Research supported by the Torsten Söderberg Foundation.