Researchers fill remaining gaps in Arabidopsis genome sequence

Arabidopsis thaliana is a species cultivated worldwide for genetic research and was the first plant to have its entire set of chromosomes (its genome) sequenced.

The initial genome sequence, published in 2000, had many gaps, but technological improvements over the next few years filled the gaps, one by one, until only two remained: large regions undefined on chromosomes 2 and 4 where the genes coding for ribosomal RNAs are repeated. in hundreds of copies.

These groups of ribosomal RNA genes, called nucleolus organizer regions (NORs), are not only difficult to define in Arabidopsis; NOR gaps remain in the genome sequences of almost all eukaryotes (organisms whose cells have a nucleus), including humans. This has blocked studies of NORs and the genes they contain, which code for the RNAs of ribosomes, the protein synthesis machines of all living cells.

Ribosomal RNA genes are regulated in ways that are not fully understood. For example, it is known that they are under epigenetic control, meaning they can be turned on or off in a way that does not depend on their sequence, but it is not clear how. And gene misregulation occurs in many cancers.

As a result, understanding ribosomal RNA gene regulation has long been the focus of biomedical research funding, which includes studies in plants, yeast, fruit flies, mice, and other organisms. models.

A new study, published in Scientists progress, reports the complete sequences of the two Arabidopsis NORs and how active and silent ribosomal RNA genes are distributed in the NORs. The paper was authored by postdoctoral researchers Dalen Fultz, Anastasia McKinlay and Ramya Enganti in the laboratory of Craig S. Pikaard, a Howard Hughes Medical Institute investigator and professor emeritus, and Carlos O. Miller Professor, in the Departments of Biology and Molecular and cellular biochemistry at Indiana University Bloomington (IUB). Previous studies from the lab have shown that active and silent ribosomal RNA gene subtypes coexist but are associated with different NORs, based on genetic testing.

The new study identified more than 70 different gene subtypes, based on subtle differences, located in either NOR2 or NOR4, but not both. Knowing the physical positions of all of these subtypes, the authors performed tests to determine whether each subtype was activated, to produce ribosomal RNA, or deactivated. They also tested what happens in genetic mutants that are unable to silence their ribosomal RNA genes.

They found that one NOR is almost completely inhibited in growing plants, while the other NOR accounts for almost all ribosomal RNA gene activity, but only in its central region. It was found that regions of high genetic activity correlate with regions where chemical modification of DNA (by addition of methyl groups to a single carbon) is low and where neighboring genes tend to be of the same sub -kind.

The results provide a first insight into how ribosomal RNA genes are organized and regulated in the context of full-length NORs. Since NOR activity also differs in other species, including humans and fruit flies, plant studies provide information of great biomedical relevance. The studies also pave the way for future studies in Arabidopsis aimed at understanding the epigenetic control and evolution of NOR, particularly the newly identified correlation between gene activity and gene subtype homogenization.