As a first approximation, genes can be defined as stretches of DNA that encode a single protein or a single functional RNA, such as an rRNA or tRNA. There are exceptions to this rule because there are mechanisms, such as alternative splicing of the primary RNA transcript into different mRNAs, that may intervene between a given gene and a finished protein. As a result, in some cases a single gene may actually encode multiple proteins.
[...] Understanding how CREB activation by extracellular stimuli leads to the altered expression of target genes that lead to the formation of memory in the hippocampus, or aspects of addiction in the nucleus accumbens and locus coeruleus, are currently areas of intense research. Overall, the mechanisms underlying the many forms of plasticity of which the nervous system is capable are likely to be quite complex, involving a multitude of different target genes and many different types of regulation. Nevertheless, CREB appears to be important, and also provides a good model to understand the role of gene expression in long- term changes in neural function. [...]
[...] The spliced mRNA leaves the nucleus and binds to a ribosome in the cytoplasm where it can direct the synthesis of a protein; however, the entire mature mRNA is not translated. All mRNAs contain untranslated flanking sequences at their ends. Many genes contain multiple introns and exons that may not be spliced identically in every cell type or in a given cell type at every stage of development. This mechanism, alternative splicing, can produce functionally very different forms of a protein or even entirely different proteins from a single gene. [...]
[...] The terminology is somewhat problematic because many cellular genes are induced independently of protein synthesis, but with a time course intermediate between classic IEGs and late-response genes. Some genes may be regulated with different time courses or requirements for protein synthesis in response to different extracellular signals. Moreover, many cellular genes regulated as IEGs encode proteins that are not transcription factors. Despite these caveats, the concept of IEG-encoded transcription factors in the nervous system has provided a useful heuristic for understanding cascades of gene regulation. [...]
[...] Many and possibly most genes contain cis-regulatory elements that confer responsiveness to such physiological signals. Such cis-elements are called response elements. Response elements work by binding transcription factors that are activated (or inhibited) in response to specific physiological signals, such as second messenger–dependent phosphorylation, steroid hormone binding, or drugs. Many examples of transcription factors activated by physiological and pharmacological signals are now known. A small number of these will be described because of their relevance to neural plasticity, including the action of psychotropic drugs. [...]
[...] Along with neurotransmitters another important intracellular signaling mechanism are the steroid hormones, such as cortisol, which are released in response to stress. Both second messenger systems and steroid hormones regulate the expression of genes in the cell nucleus. Some second messengers may actually enter the cell nucleus. In most cases, however, they modify the function of another protein such as a protein kinase, which enters the nucleus and interacts with transcription factors that directly or indirectly bind to DNA. Steroid hormones are lipophilic molecules that cross the cell membrane and bind a receptor in the cytoplasm. [...]
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