Hello,
Some recent published literature has detailed pathophysiology of nuclear speckles aka ‘nuclear dots’
I will list the primary articles for your reading and learning:
original study in 2000 that used intrinsic mutation in osteogenesis imperfecta to look at role of splicing with respect to nuclear structure Tracking Col1a1 RNA in Osteogenesis Imperfecta: Splice-Defective Transcripts Initiate Transport from the Gene but Are Retained within the Sc35 Domain - PMC
Primary scaffolding genes observed: SON and SRRM2 are essential for nuclear speckle formation | eLife
study of SON-dependent nuclear speckle rehabilitation in protieinopathies SON-dependent nuclear speckle rehabilitation alleviates proteinopathies | Nature Communications → this is followed by a recent clinical trial using a pinworm therapy which affects nuclear speckle spherical surface tension for disease modification
spatialtemporal resolution of nuclear speckle periphery and introns centered on RNA and mitosis The periphery of nuclear speckles defines a spatially and temporally regulated compartment of long-lived intron-retained RNAs that resolves during mitosis | Nature Cell Biology
https://www.cell.com/neuron/fulltext/S0896-6273(21)00196-3 Tau
GC https://www.cell.com/cell/fulltext/S0092-8674(26)00098-X
HSV activation https://www.pnas.org/doi/10.1073/pnas.2511555123
Renal cell carcinoma https://www.pnas.org/doi/10.1073/pnas.2511555123
Review https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(26)00059-0
In the meanwhile, I was also was considering whether profiling these ‘nuclear dots’ would have utility in reference to spaceflight. I sent this idea to some of the AWG leads for feedback, some of which includes the need for imaging - if this remains the main bottleneck to publisheable analysis, then at least there are references for the AWG/self-learning. If anyone else has feedback because of familiarity with nuclear speckles, including past research then comments are obviously welcome. Essentially, while early nuclear speckle studies used electron microscopy and antibodies/SDS-page to profile these structures, whole genome profiling has enabled investigators to identify critical genes that are expressed with nuclear speckles and presumably these could be identified with DEG in parallel to gene ontology to characterize murine/rat and/or human samples in spaceflight as well as ground studies comparing control vs radiation only vs simulated microgravity only vs combined experimental conditions → additionally literature has implicated the presence of high GC content and introns in said structures as well as alternative splicing (would use splicing aware software); this could also by studied with methylation analysis; feedback is welcome
differential splicing software that can be coupled with splicing aware: Differential Alternative Splicing Analysis with rMATS - BTEP Coding Club