GIMM researchers review the latest advances in our understanding of nuclear speckles, structures within the cell nucleus that are revealing a far more active role in how genetic information is processed.
For many years, nuclear speckles were regarded primarily as sites where cells concentrate and store molecules required for RNA processing. Today, that view is changing.
In a new review article, ‘Nuclear speckles: New insights into structure and function’, published in Current Opinion in Structural Biology, GIMM researchers André Ventura-Gomes, Rui Sousa-Luís and Maria Carmo-Fonseca bring together recent advances in our understanding of the structure and function of these biomolecular condensates and highlight their emerging role as important regulators of gene expression.
When location inside the cell matters
When a gene is activated, the information encoded in DNA is first copied into a precursor RNA molecule. Before it can fulfil its function, this molecule needs to undergo several processing steps.
One of these is splicing, the process through which specific sequences, known as introns, are removed and the remaining parts of the RNA are joined together to form a mature molecule.
Research in recent years has shown that the position of genes within the nucleus can influence how efficiently this process occurs. Genes located closer to nuclear speckles have greater access to the cellular components involved in splicing, helping RNA to be processed more efficiently.
This effect appears to be particularly important for genes containing short introns rich in guanine and cytosine, two of the four bases that make up DNA.
Much more than simple “reservoirs”
Advances in imaging techniques and biophysical studies have also revealed that nuclear speckles are far more complex than previously thought.
Rather than being uniform condensates, they have a highly organised internal structure formed through multiple interactions between proteins and RNA molecules. This organisation may help cells concentrate different components of the molecular machinery where and when they are needed.
And their role does not end with splicing. The evidence reviewed by the researchers suggests that nuclear speckles are involved in several stages of an RNA molecule’s life, from processing and quality control to the retention of molecules that are not yet ready and the subsequent export of mature RNA from the nucleus to the cytoplasm.
Rethinking the organisation of the nucleus
These advances are changing the way scientists understand the organisation of the cell nucleus. Rather than simply occupying different regions, the position of genes and the structures surrounding them may actively contribute to determining how genetic information is used by cells.
Many questions, however, remain unanswered. Alterations in nuclear speckle organisation have been associated with several diseases, including neurodegenerative disorders, but further research is needed to understand how these changes contribute directly to disease development.
By bringing together the latest knowledge in the field, the review by André Ventura-Gomes, Rui Sousa-Luís and Maria Carmo-Fonseca highlights nuclear speckles as key players in coordinating RNA processing and gene expression, while opening new questions about the relationship between nuclear architecture, cellular function and disease.