Both transcriptional and post-transcriptional regulations are pivotal in balancing the constitutive and low-level HSC turnover and downstream differentiation and hematopoietic reconstitution. In multicellular organisms, alternative splicing is a key post-transcriptional regulation mechanism that expands transcript ...
RNA splicing is catalyzed by the spliceosome, a large ribonucleoprotein complex that contains five small nuclear RNAs (snRNAs) and over 200 proteins. The noncoding snRNAs base-pair with specific sequences in the pre-mRNA that mark the ends of introns. The snRNAs, not the spliceosomal proteins,...
Furthermore, by leveraging the enhanced sensitivity of MYC-driven tumors to splicing perturbations, researchers identified synthetic lethal genes for MYC such as BUD31, which is a component of the core spliceosome [46]. Depletion of BUD31 expression in MYC-driven breast cancer cells resulted in ...
Genetic and functional data indicate that RNA splicing factors can act as oncoproteins as well as tumour suppressors. A subset of RNA splicing factors are recurrent targets of specific point mutations in cancer. Many other splicing factors exhibit dysregulated expression in cancer. In many cases, rec...
Understanding the molecular mechanism of protein-RNA recognition and formation of protein-RNA complexes is a major challenge in structural biology. Unfortunately, the experimental determination of protein-RNA complexes is tedious and difficult, both by X-ray crystallography and NMR. For many interacting ...
Alternative splicing of pre-mRNAs provides an additional mechanism whereby genetic variation can create functional diversity across human genomes. Rare mutations and common variants that influence pre-mRNA splicing have been linked to a broad range of human diseases [15,16,17]. The effects of genetic...
G-mediated splicing is due to the role of CBC in recruiting snRNPs and spliceosome assembly. As discussed above, cap-dependent translation initiation is mediated by the cap-binding protein eIF4E. The eIF4E affinity to the m7G cap was enhanced by the interaction of eIF4G peptides with the ...
is done on populations of cells (bulk RNA-seq) and increasingly with single-cell or single-nucleus resolution (scRNA-seq). Choosing a suitable RNA-seq method for a particular biological question depends on many aspects, but the number of samples that can be analyzed is almost always a ...
The ubiquity of RNA-seq has led to many methods that use RNA-seq data to analyze variations in RNA splicing. However, available methods are not well suited for handling heterogeneous and large datasets. Such datasets scale to thousands of samples across dozens of experimental conditions, exhibit ...
RNA sequencing revealed that AMA impaired transcription and RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing molecule. The impairment in RNA splicing and PL ratio was rescued by overexpresion of hnRNP that had been also affected by transcriptional repression. Fly ...