Histone genes differ from other eucaryotic genes in that they lack introns and are not polyadenylated. The levels of histone mRNAs are coordinately regulated with DNA synthesis. mRNA stability is a major determinant of histone mRNA levels and histone mRNAs are rapidly degraded when DNA synthesis is inhibited. This thesis examines sequence requirements for both processing and degradation of histone mRNA. The highly conserved terminal stem-loop of the histone mRNA is necessary and sufficient to mediate regulated degradation and is also necessary for processing the 3$\sp\prime$ end of the histone mRNA. Histone mRNAs are degraded during translation and the stem-loop must be less than 300 nucleotides downstream of the termination codon for proper regulation of degradation. No particular sequence in the 4-base loop of the stem-loop is necessary for proper degradation since RNAs with changes in the sequence of these bases are regulated normally. A disruption of the base pair at the top of the stem however abolishes regulation of degradation and the mRNA is stable when DNA synthesis is inhibited. Changes in the sequence of the bases of the loop also caused the mRNA to be processed inefficiently. Taken together, these data suggest that degradation occurs on the ribosome and that the stem-loop structure is specifically recognized. A wild type loop sequence is not sufficient for efficient processing since a gene with the terminal stem-loop at the end of histone mRNA has multiple functions in histone mRNA metabolism. A link between the lack of introns in histone genes and lack of polyadenylation of histone mRNAs has been demonstrated. Thus introduction of intron(s) into the histone H2a gene interferes with 3$\sp\prime$ end formation resulting in substantial reduction in the amount of histone mRNA with a terminal stem-loop and a parallel increase in the amount of / polyadenylated histone mRNA. It is proposed that this occurs because a nascent spliceosome directs 3$\sp\prime$ end formation. / Source: Dissertation Abstracts International, Volume: 51-04, Section: B, page: 1605. / Major Professor: William F. Marzluff. / Thesis (Ph.D.)--The Florida State University, 1990.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_78251 |
| Contributors | Pandey, Niranjan Babu., Florida State University |
| Source Sets | Florida State University |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | 210 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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