A molecular and genetic study of mammalian ribosomal protein (rprotein) genes is described. The approach outlined involves well-characterized panels of mammalian rprotein cDNAs, human genomic and cDNA libraries and Chinese hamster cell ribosomal protein mutants.
Four specific aims are indicated. 1. Mutant and wildtype rprotein genes will be sequenced. Differences among these structures should indicate the molecular nature of somatic mutations as well as limits of polymorphism compatible with ribosome assembly and function. 2. Fourteen ribosomal genes (for which cDNA probes are available) will be mapped on human chromosomes using appropriate human x rodent cell hybrids. Chromosomal organization of rprotein genes can provide clues to mechanisms regulating the gene family and to its evolutionary history. 3. The arrangement and nucleic acid sequences of several human and other species' rprotein genes will be determined. Structures shared by heterologous human genes can suggest mechanisms that regulate the gene family. Differences among analogous genes from phylogenetic series of animals should permit construction of a ribosomal protein gene evolutionary history. 4. rProtein cDNA probes and genomic DNA clones will be used to analyze transcription, messenger processing and mRNA turnover in cultured animal cells. In particular, effects of gene dosage and organization on ribosomal gene regulation will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM023013-11
Application #
3271464
Study Section
(SSS)
Project Start
1977-09-16
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
11
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Kansas State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Manhattan
State
KS
Country
United States
Zip Code
66506
Martin-Nieto, J; Roufa, D J (1997) Functional analysis of human RPS14 null alleles. J Cell Sci 110 ( Pt 8):955-63
Xu, W B; Roufa, D J (1996) The gene encoding human ribosomal protein S24 and tissue-specific expression of differentially spliced mRNAs. Gene 169:257-62
Tasheva, E S; Roufa, D J (1995) A densely methylated DNA island is associated with a chromosomal replication origin in the human RPS14 locus. Somat Cell Mol Genet 21:369-83
Tasheva, E S; Roufa, D J (1995) Regulation of human RPS14 transcription by intronic antisense RNAs and ribosomal protein S14. Genes Dev 9:304-16
Tasheva, E S; Roufa, D J (1994) A mammalian origin of bidirectional DNA replication within the Chinese hamster RPS14 locus. Mol Cell Biol 14:5628-35
Tasheva, E S; Roufa, D J (1994) Densely methylated DNA islands in mammalian chromosomal replication origins. Mol Cell Biol 14:5636-44
Overman, P F; Rhoads, D D; Tasheva, E S et al. (1993) Multiple regulatory elements ensure accurate transcription of a human ribosomal protein gene. Somat Cell Mol Genet 19:347-62
Tasheva, E S; Roufa, D J (1993) Deoxycytidine methylation and the origin of spontaneous transition mutations in mammalian cells. Somat Cell Mol Genet 19:275-83
Diaz, J J; Roufa, D J (1992) Fine-structure map of the human ribosomal protein gene RPS14. Mol Cell Biol 12:1680-6
Diaz, J J; Rhoads, D D; Roufa, D J (1991) PCR-mediated chemical mutagenesis of cloned duplex DNAs. Biotechniques 11:204-6, 208, 210-1

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