Cis-regulatory element
Encyclopedia
A cis-regulatory element or cis-element is a region of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 that regulates the expression of genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...

 located on that same molecule of DNA (often a chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

). This term is constructed from the Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

 word cis, which means "on the same side as". These cis-regulatory elements are often binding sites for one or more trans-acting factors. A cis-element may be located 5' to the coding sequence of the gene it controls (in the promoter region or further upstream), in an intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...

, or 3' to the gene's coding sequence, either in the untranslated or untranscribed region.

An example of a cis-acting regulatory sequence is the operator in the lac operon
Lac operon
The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...

. This DNA sequence is bound by the lac repressor
Lac repressor
The lac repressor is a DNA-binding protein which inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria. These genes are repressed when lactose is not available to the cell, ensuring that the bacterium only invests energy in the production of...

, which, in turn, prevents transcription of the adjacent genes on the same DNA molecule. The lac operator is, thus, considered to "act in cis" on the regulation of the nearby genes. The operator itself does not code for any protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

.

In contrast, trans-regulatory element
Trans-regulatory element
Trans-regulatory elements are genes which may modify the expression of distant genes. More specifically, trans-regulatory elements are DNA sequences that encode transcription factors....

s are diffusible factors, usually proteins, that may modify the expression of genes distant from the gene that was originally transcribed to create them. For example, a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

 which regulates a gene on chromosome 6 might itself have been transcribed from a gene on chromosome 11. This term is constructed from the Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

 root trans, which means "across from".

To summarize, cis-regulatory elements are present on the same molecule of DNA as the gene they regulate whereas trans-regulatory elements can regulate genes distant from the gene from which they were transcribed.

Examples of cis-regulatory elements in RNA

RNA elements
Type Abbr. Function Distribution Ref.
Frameshift element
Translational frameshift
Translational frameshifting or ribosomal frameshifting refers to an alternate process of protein translation. A protein is translated from one end of the mRNA to the other, from the 5' to the 3' end. Normally a protein is translated from a template mRNA with consecutive blocks of 3 nucleotides...

 
Regulates alternative frame use with messenger RNAs Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

, Bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, Eukaryota
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

, RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

es
Iron response element
Iron response element
The Iron response element or Iron-responsive element is a short conserved stem-loop which is bound by iron response proteins . The IRE is found in UTRs of various mRNAs whose products are involved in iron metabolism. For example, the mRNA of ferritin contains one IRE in its 5' UTR...

 
IRE Regulates the expression of iron associated genes Eukaryota 
Leader peptide
Attenuator (genetics)
Attenuation is a regulatory feature found throughout Archaea and Bacteria causing premature termination of transcription. Attenuators are 5'-cis acting regulatory regions which fold into one of two alternative RNA structures which determine the success of transcription...

 
Regulates transcription of associated genes and/or operons Bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 
Internal ribosome entry site
Internal ribosome entry site
An internal ribosome entry site, abbreviated IRES, is a nucleotide sequence that allows for translation initiation in the middle of a messenger RNA sequence as part of the greater process of protein synthesis...

 
IRES Initiates translation in the middle of a messenger RNA RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

, Eukaryota 
Pyrrolysine insertion sequence
PYLIS downstream sequence
In biology, the PYLIS downstream sequence is a stem-loop structure which appears on some mRNA sequences. This structural motif causes the UAG stop codon to be translated to the amino acid pyrrolysine instead of ending the protein translation...

 
PYLIS directs the cell to translate immediately adjacent UAG stop codon
Stop codon
In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals a termination of translation. Proteins are based on polypeptides, which are unique sequences of amino acids. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide...

s into pyrrolysine
Pyrrolysine
Pyrrolysine is a naturally occurring, genetically coded amino acid used by some methanogenic archaea and one known bacterium in enzymes that are part of their methane-producing metabolism. It is similar to lysine, but with an added pyrroline ring linked to the end of the lysine side chain...

 
Archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...

 
Riboswitch
Riboswitch
In molecular biology, a riboswitch is a part of an mRNA molecule that can directly bind a small target molecule, and whose binding of the target affects the gene's activity. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the...

 
Gene regulation Bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, Eukaryota 
Selenocysteine insertion sequence
SECIS element
In biology, the SECIS element is an RNA element around 60 nucleotides in length that adopts a stem-loop structure. This structural motif directs the cell to translate UGA codons as selenocysteines...

 
SECIS directs the cell to translate UGA stop-codons as selenocysteine
Selenocysteine
Selenocysteine is an amino acid that is present in several enzymes .-Nomenclature:...

s
Metazoa 

See also

  • DNA
    • TATA box
      TATA box
      The TATA box is a DNA sequence found in the promoter region of genes in archaea and eukaryotes; approximately 24% of human genes contain a TATA box within the core promoter....

    • Pribnow box
      Pribnow box
      The Pribnow box is the sequence TATAAT of six nucleotides that is an essential part of a promoter site on DNA for transcription to occur in bacteria...

    • SOS box
      SOS box
      SOS box is the region in the promoter of various genes to which the LexA repressor binds to repress the transcription in the absence of DNA damage.-Examples:See Nucleic acid nomenclature for an explanation of non-GATC nucleotide letters...

    • CAAT box
      CAAT box
      In molecular biology, a CCAAT box is a distinct pattern of nucleotides with GGCCAATCT consensus sequence that occur upstream by 75-80 bases to the initial transcription site. The CAAT box signals the binding site for the RNA transcription factor, and is typically accompanied by a conserved...

    • CCAAT box
    • Operator (biology)
      Operator (biology)
      In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...

    • Upstream Activation Sequence
  • RNA
    • List of cis-regulatory RNA elements
    • Polyadenylation
      Polyadenylation
      Polyadenylation is the addition of a poly tail to an RNA molecule. The poly tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA for translation...

       signals, mRNA
    • AU-rich element
      AU-rich element
      AU-rich elements are one of the most common types of regulatory elements found in mRNAs. They are involved in the control of gene expression. They are the most common determinant of RNA stability in mammalian cells....

      , mRNA
  • Other
    • Regulation of gene expression
      Regulation of gene expression
      Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...

    • cis-regulatory module
      Cis-regulatory module
      Cis-regulatory module is a stretch of DNA, usually 100-1000 DNA base pairs in length, where a number of transcription factors can bind and regulate expression of nearby genes. One cis-regulatory element can regulate several genes, and conversely, one gene can have several cis-regulatory modules...

    • Gene regulatory network
      Gene regulatory network
      A gene regulatory network or genetic regulatory network is a collection of DNA segments in a cell whichinteract with each other indirectly and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA.In general, each mRNA molecule goes...

    • Operon
      Operon
      In genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...

    • Promoter
    • Trans-acting factor
    • Rfam
      Rfam
      Rfam is a database containing information about non-coding RNA families and other structured RNA elements. It is an annotated, open access database hosted by the Wellcome Trust Sanger Institute in collaboration with Janelia Farm...

    • Transterm
      Transterm
      Transterm is a database of mRNA sequences, codon usage, and associated cis-regulatory elements that regulate gene expression. Many of these elements are in the 3' UTR.- References :...

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