Furthermore, alternative processing of transcripts can be influenced by the nature of transcriptional promoters and by transcription factors through two mechanisms ( 4, 8 – 10). It has been shown that the recruitment of processing factors and the maturation of pre-mRNAs occur at least in part cotranscriptionally and are enhanced by RNA polymerase II (Pol II) and its phosphorylation ( 5 – 7). It is now widely accepted that pre-mRNA splicing and 3′-end maturation are tightly connected to transcription in Metazoans and that transcription impacts RNA processing ( 4, 5). Moreover, the role of another level of splicing regulation that involves transcriptional regulators has not been investigated yet. However, only few splicing factors have been found to be altered in cancer. In some cases, cancer-associated deregulation of alternative splicing arises from mutations within splicing regulatory sequences or from alterations of the expression of splicing factors involved in splicing regulation ( 2, 3). Genes involved in major cellular programs often give rise to splice isoforms with distinct biological activities and deregulated expression in cancer ( 2, 3). Indeed, most human genes give rise to several transcripts with different exon content because of alternative splicing and alternative cleavage/polyadenylation sites ( 1). A second level of gene expression that is often altered in cancer cells is pre-mRNA splicing. Gene expression in cancer cells is altered at the transcriptional level by many mutated oncogenes acting as transcriptional regulators. These data show that elevated expression of a splice isoform in cancer can be due to an alteration of the transcription process by a mutated transcriptional regulator and provide evidence for a physio/pathological impact of the coupling between transcription and mRNA maturation. The endogenous D1b protein is enriched in nuclei, where the oncogenic activity of cyclin D1 is known to occur, and depleting D1b in addition to D1a results in a stronger reduction of EwSa cell growth than depleting D1a only. As a result, the D1b/D1a ratio is elevated in EwSa cell lines and tumors. Detailed analyses of RNA polymerase dynamics along the gene and of the effects of an inhibitor of elongation show that EWS-FLI1 favors D1b isoform expression by decreasing the elongation rate, whereas EWS has opposite effects. We show that, although both EWS and EWS-FLI1 enhance cyclin D1 gene expression, they regulate the D1b/D1a transcript ratio in an opposite manner. EWS-FLI1 directly stimulates transcription of the CCND1 protooncogene encoding cyclin D1a and a less abundant but more oncogenic splice isoform, D1b. In particular, the Ewing sarcoma (EwSa) oncogene, resulting from a fusion of the EWS and FLI1 genes, encodes a well characterized transcription factor. In cancer, where splice variant expression is often deregulated, many mutated oncogenes are transcriptional regulators. However, whether this regulatory mechanism has a physio/pathological impact is not known. I would be clear where the configuration of the threads has been defined, and the 1D, 2D and 3D access pattern depends on how you are interpreting your data and also how you are accessing them by 1D, 2D and 3D blocks of threads.Pre-mRNA splicing and polyadenylation are tightly connected to transcription, and transcriptional stimuli and elongation dynamics can affect mRNA maturation. To sumup, it does it matter if you use a dim3 structure. Int y = blockIdx.y * blockDim.y + threadIdx.y īecause blockIdx.y and threadIdx.y will be zero. So, in both cases: dim3 blockDims(512) and myKernel>(.) you will always have access to threadIdx.y and threadIdx.z.Īs the thread ids start at zero, you can calculate a memory position as a row major order using also the ydimension: int x = blockIdx.x * blockDim.x + threadIdx.x The same happens for the blocks and the grid. When defining a variable of type dim3, any component left unspecified is initialized to 1. However, the access pattern depends on how you are interpreting your data and also how you are accessing them by 1D, 2D and 3D blocks of threads.ĭim3 is an integer vector type based on uint3 that is used to specify dimensions. ![]() ![]() The memory is always a 1D continuous space of bytes. The way you arrange the data in memory is independently on how you would configure the threads of your kernel.
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