Biology Reference
In-Depth Information
4.2 Mutations that Affect the Flow of Information
from DNA to RNA
The process of hearing, as well as development of the hearing organ, occurs
as the result of a programmed expression of genes. As a result, the tissues
of the ear are sensitive to alterations in all aspects of the process of tran-
scription of DNA into mRNA. Mutations have been found in transcription
factors that program ear development. In addition, deafness results from
mutations that alter the mRNA expression of individual genes essential for
hearing. These mutations include alterations in the gene promotors and in
the mRNA splicing sites. Without a functional promoter, genes are not
properly transcribed. As a result of promoter mutations, a gene may be
expressed at a lower level than normal or expression in critical tissues may
simply be lost. The lack of sufficient transcript often results in a decrease
in final protein levels. This lack of protein may, in turn, result in deafness
if this protein is critical for ear development, or for neurosensory function.
In addition, mutations have been observed that allow for gene transcrip-
tion, but result in mRNA degradation such that, in the end, no protein is
produced.
4.2.1 Transcription Factor Mutations Lead to Hearing Loss
Mutations in transcription factors have been found to be the basis for both
syndromic and nonsyndromic deafness. Transcription factors are a group of
proteins that bind DNA and initiate transcription at specific sites on the
DNA (Fig. 2.7). Eukaryotic genes require several types of transcription
factors in order to be transcribed. The genes for these transcription factors
may be close to the genes they regulate, or far away. They recognize the
FIGURE 2.7. Initiation of RNA transcription. To initiate gene transcription, the pro-
moter of the gene is bound by a series of transcription factors that recognize
specific sequences in the promoter DNA. Transactivators then join the complex by
binding to specific sites on the transcription factors. This assemblage of transcrip-
tional regulators recruits RNA polymerase, and RNA transcription is begun.
