A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and transported into the cytoplasm, serving as a template for protein synthesis during translation. In prokaryotes, which lack a nucleus, the processes of transcription and translation occur at the same location and almost simultaneously since the newly-formed mRNA is susceptible to rapid degradation.
Gene Expression Can Be Regulated at Any Stage during Transcription
Every cell of an organism contains the same DNA and, consequently, the same set of genes. However, not all genes in a cell are "turned on" or used to synthesize proteins. A gene is said to be expressed when the protein it encodes is produced by the cell. Gene expression is regulated to ensure the proper generation of proteins in specific cells at specific times. Various intrinsic and extrinsic mechanisms regulate gene expression before and during transcription.
The structure of chromatin—compacted DNA and its associated histone proteins—can be chemically modified to be open or closed. Such modifications allow or restrict access to the DNA by the transcriptional machinery. Chromatin modification is an intrinsic mechanism employed during development to form different cell types (e.g., neuron versus muscle cell) from the same genome.
DNA-binding proteins, called transcription factors, regulate transcription by binding to specific DNA sequences near or within the coding regions of genes. Transcription factors that promote the initiation of transcription are called activators. Proteins that prevent the transcription machinery from binding to the transcription initiation site are called repressors. Transcriptional activators or repressors respond to external stimuli such as signaling molecules, nutritional deficiencies, temperature, and oxygen.
Gene Expression Can Be Post-transcriptionally and Post-translationally Regulated
Gene expression can be regulated by post-transcriptional mRNA processing. In eukaryotes, transcribed mRNA undergoes splicing and other modifications that protect the ends of the RNA strand from degradation. Splicing removes introns—segments that do not encode proteins—and joins the protein-coding regions called exons. Alternative splicing allows for the expression of functionally diverse proteins from the same gene. Regulation of gene expression by alternative splicing plays an important role in organ development, cell survival and proliferation, and adaptation to environmental factors.
Gene expression can also be altered by regulating the translation of mRNA into proteins. Translation can be regulated by microRNAs—small, non-coding RNAs—that bind to a specific mRNA sequence and block the initiation of translation or degrade the transcribed mRNA. In addition, proteins called translational repressors can bind to RNA and interfere with translation initiation.
Translated polypeptides undergo processing to form functional proteins. The addition or removal of chemical groups can alter the activity, stability, and localization. For instance, adding or removing phosphate groups can activate or inactivate proteins. Similarly, the addition of ubiquitin groups causes protein degradation. Thus, post-translational protein modifications are the final stage of gene regulation.
