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==Related diseases== Research has also led to greater knowledge about certain diseases related to changes within primary transcripts. One study involved [[estrogen receptor]]s and differential splicing. The article entitled, "Alternative splicing of the human estrogen receptor alpha primary transcript: mechanisms of exon skipping" by Paola Ferro, Alessandra Forlani, Marco Muselli and Ulrich Pfeffer from the laboratory of Molecular Oncology at National Cancer Research Institute in Genoa, Italy, explains that 1785 nucleotides of the region in the DNA that codes for the estrogen receptor alpha (ER-alpha) are spread over a region that holds more than 300,000 nucleotides in the primary transcript. Splicing of this pre-mRNA frequently leads to variants or different kinds of the mRNA lacking one or more exons or regions necessary for coding proteins. These variants have been associated with [[breast cancer]] progression.<ref>{{cite journal | vauthors = Ferro P, Forlani A, Muselli M, Pfeffer U | title = Alternative splicing of the human estrogen receptor alpha primary transcript: mechanisms of exon skipping | journal = International Journal of Molecular Medicine | volume = 12 | issue = 3 | pages = 355β63 | date = September 2003 | pmid = 12883652 }}</ref> In the life cycle of [[retrovirus]]es, proviral DNA is incorporated in transcription of the DNA of the cell being infected. Since retroviruses need to change their pre-mRNA into DNA so that this DNA can be integrated within the DNA of the host it is affecting, the formation of that DNA template is a vital step for retrovirus replication. Cell type, the differentiation or changed state of the cell, and the physiological state of the cell, result in a significant change in the availability and activity of certain factors necessary for transcription. These variables create a wide range of viral gene expression. For example, tissue culture cells actively producing infectious virions of avian or murine [[leukemia]] viruses (ASLV or MLV) contain such high levels of viral RNA that 5β10% of the mRNA in a cell can be of viral origin. This shows that the primary transcripts produced by these retroviruses do not always follow the normal path to protein production and convert back into DNA in order to multiply and expand.<ref>{{cite book | veditors = Coffin JM, Hughes SH, Varmus HE | chapter = Transcription | title = Retroviruses | location = Cold Spring Harbor (NY) | publisher = Cold Spring Harbor Laboratory Press | date = 1997 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK19441/ }}</ref>
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