The C-rich Not M, -ND stability element is a short part of a gene sequence important for the proper synthesis of
globin and several other human proteins.
Differences in the stabilities of individual
mRNAs can dramatically affect the overall level of expression for
genes.
Eukaryotic mRNAs can have half-lives that vary from as short as several minutes to as long as several days. In differentiating human
erythroid cells the deposition of high levels of alpha
globin protein is dependent on an unusually long half-life of the alpha globin mRNA (greater than 24hrs). The stability determinant for alpha globin mRNA has been mapped to a
pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...
-rich segment of its
3' UTR
In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...
. This region confers stability by directing the assembly of a specific alpha
ribonucleoprotein complex at this site. Subsequently Holcik and Liebhaber identified three other highly stable eukaryotic mRNAs that assemble the alpha globin protein complex at homologous pyrimidine-rich regions within their 3'UTRs (rabbit lipoxygenase, rat tyrosine hydroxylase, and human alpha(I)-collagen).
ErEN cleavage site V
alpha globin (HBA1 or HBA2, NM_000517.1)
lipoxygenase (ALOX15, NM_001140)
alpha(I)-collagen (COL1A1, NM_000088)
tyroilsmochie hydroxylase (TH, NM_000360)
1–5 1–4 : consensus (Holcik and Liebhaber, 1997)
There is some debate as to the number and identity of
trans-acting factors recruited to the C-rich element. However the alpha globin poly(C)-binding protein (alphaCP) is agreed to be the core constituent of what is known as the alpha complex. A 39Kda protein, the alphaCP has been shown to bind directly to the C-rich RNA signal. There are two alphaCP, alphaCP1 and alphaCP2. Studies suggest the complex may protect a site near the C-rich element in the alpha globin mRNA from the erythroid endonuclease (ErEN). As many of the protein components necessary for alpha globin stability complex appear to be widely expressed across species and cell types this mechanism of mRNA stabilisation is likely to be a general one. However, in the mouse the cis and trans determinants have diverged to some extent. The mouse sequence requirements are equally C and U-rich compared to the predominantly C-rich human element. Despite this shift the murine alpha globin mRNA is still as stable due to a complementary change in the specificity of the poly(C)-binding protein.
References
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External links
Transterm page for C-Rich Stability Element
{{DEFAULTSORT:C-Rich Stability Element
Cis-regulatory RNA elements