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Judith Lengyel and Sheldon Penman from the department of Biology at the [[Massachusetts Institute of Technology]] (MIT) in Cambridge, Massachusetts wrote an article about one type of primary transcript involved in the genes of two [[dipteran]]s, or insects that have two wings: ''[[Drosophila]]'' and ''[[Aedes]]''. The article describes how researchers looked at hnRNA, or basically pre-mRNA, primary transcripts in the two kinds of insects. The size of hnRNA transcripts and the fraction of hnRNA that is converted to mRNA in cell lines, or groups of cells derived from a single cell of whatever one is studying, of ''Drosophila melanogaster'' and ''Aedes albopictus'' were compared. Both insects are dipterans, but ''Aedes'' has a larger genome than ''Drosophila''. This means that Aedes has more DNA, which means more genes. The ''Aedes'' line make larger hnRNA than did the ''Drosophila'' line even though the two cell lines grew under similar conditions and produced mature or processed mRNA of the same size and sequence complexity. These data suggest that the size of hnRNA increases with increasing genome size, which is obviously shown by Aedes.<ref>{{cite journal | vauthors = Lengyel J, Penman S | title = hnRNA size and processing as related to different DNA content in two dipterans: Drosophila and Aedes | journal = Cell | volume = 5 | issue = 3 | pages = 281–90 | date = July 1975 | pmid = 807333 | doi = 10.1016/0092-8674(75)90103-8 | s2cid = 39038640 }}</ref>
Ivo Melcak, Stepanka Melcakova, Vojtech Kopsky, Jaromıra Vecerova and Ivan Raska from the department of Cell Biology at the Institute of Experimental Medicine, at the Academy of Sciences of Czech Republic in Prague studied the influences of [[nuclear speckles]] on pre-mRNA. Nuclear speckles (speckles) are a part of the nuclei of cells and are enriched with [[splicing factor]]s known for involvement in mRNA processing. Nuclear speckles have shown to serve neighboring active genes as storage places of these splicing factors. In this study, researchers showed that, in HeLa cells which derived from cells of a person who had cervical cancer and have proven useful for experiments, the first group of [[spliceosome]]s on pre-mRNA come from these speckles. Researchers used microinjections of spliceosome-accepting and mutant [[adenovirus]] pre-mRNAs with differential splicing factor binding to make different groups and then followed the sites in which they were heavily present. Spliceosome-accepting pre-mRNAs were rapidly targeted into the speckles, but the targeting was found to be temperature-dependent. The [[polypyrimidine tract]] sequences in mRNA promote the construction of spliceosome groups and is required for targeting, but, by itself, was not sufficient. The downstream flanking sequences were particularly important for the targeting of the mutant pre-mRNAs in the speckles. In supportive experiments, the behavior of the speckles was followed after the microinjection of antisense deoxyoligoribonucleotides (complementary sequences of DNA and or RNA to a specific sequence) and, in this case, specific sequences of [[snRNA]]s. snRNAs are known for helping in the processing of pre-mRNA as well. Under these conditions, spliceosome groups formed on endogenous pre-mRNAs. Researchers concluded that the spliceosome groups on microinjected pre-mRNA form inside the speckles. Pre-mRNA targeting and buildup in the speckles is a result of the loading of splicing factors to the pre-mRNA, and the spliceosome groups gave rise to the speckled pattern observed.<ref>{{cite journal | vauthors = Melcák I, Melcáková S, Kopský V, Vecerová J, Raska I | title = Prespliceosomal assembly on microinjected precursor mRNA takes place in nuclear speckles | journal = Molecular Biology of the Cell | volume = 12 | issue = 2 | pages = 393–406 | date = February 2001 | pmid = 11179423 | doi = 10.1091/mbc.12.2.393 | citeseerx = 10.1.1.324.8865 | pmc = 30951 }}</ref> A study by Prashant Bhat and Mitchell Guttman from the Division of Biology and Biological Engineering at the [[California Institute of Technology]] studied whether gene positioning relative to speckles influences splicing outcome. Because highly transcribed, active genes are preferentially organized in the nucleus closer to nuclear speckles, they tested whether splicing efficiency, or the biochemical rate of splicing, is enhanced by a gene being physically close to a speckle. To establish a causal relationship between gene proximity to speckles and splicing efficiency, Bhat and Guttman used an artificial tethering system (MS2-MCP) to drive association of synthetic pre-mRNAs to specific nuclear locations, including speckles. By driving association of the pre-mRNA reporter to nuclear speckles, they found that recruitment to speckles significantly boosted splicing efficiency and subsequently protein levels. This result indicates that simply recruiting a pre-mRNA to a speckle is sufficient to increase splicing efficiency. <ref>{{cite journal | vauthors = Bhat, P., Chow, A., Emert, B. et al. | title = Genome organization around nuclear speckles drives mRNA splicing efficiency. | journal = Nature | volume = 629 | issue = 5 | pages = 1165–1173 | date = January 2016 | pmid = 38720076 | pmc = PMC11164319 | doi = 10.1038/s41586-024-07429-6 }}</ref>
==Related diseases==
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