Messenger RNA mRNA Is Modified at the 5 3 Ends

As mentioned above, mammalian mRNA molecules contain a 7-methylguanosine cap structure at their 5' terminal, and most have a poly(A) tail at the 3' terminal. The cap structure is added to the 5' end of the newly transcribed mRNA precursor in the nucleus prior to transport of the mRNA molecule to the cytoplasm. The 5' cap of the RNA transcript is required both for efficient translation initiation and protection of the 5' end of mRNA from attack by 5' ^ 3' exonu-cleases. The secondary methylations of mRNA molecules, those on the 2'-hydroxy and the N6 of adenylyl residues, occur after the mRNA molecule has appeared in the cytoplasm.

Poly(A) tails are added to the 3' end of mRNA molecules in a posttranscriptional processing step. The mRNA is first cleaved about 20 nucleotides downstream from an AAUAA recognition sequence. Another enzyme, poly(A) polymerase, adds a poly(A) tail which is subsequently extended to as many as 200 A residues. The poly(A) tail appears to protect the 3' end of mRNA from 3' ^ 5' exonuclease attack. The presence or absence of the poly(A) tail does not determine whether a precursor molecule in the nucleus appears in the cytoplasm, because all poly(A)-tailed hnRNA molecules do not contribute to cytoplasmic mRNA, nor do all cytoplasmic mRNA molecules contain poly(A) tails

B cell/pituitary —| ^ ^ TT""! F~~~n "TUf "~~Tl~n~r("i I-

Figure 37-14. Alternative promoter use in the liver and pancreatic B cell glucokinase genes. Differential regulation of the glucokinase (GK) gene is accomplished by the use of tissue-specific promoters. The B cell GK gene promoter and exon IB are located about 30 kbp upstream from the liver promoter and exon 1L. Each promoter has a unique structure and is regulated differently. Exons 2-10 are identical in the two genes, and the GK proteins encoded by the liver and B cell mRNAs have identical kinetic properties.

(the histones are most notable in this regard). Cytoplas-mic enzymes in mammalian cells can both add and remove adenylyl residues from the poly(A) tails; this process has been associated with an alteration of mRNA stability and translatability.

The size of some cytoplasmic mRNA molecules, even after the poly(A) tail is removed, is still considerably greater than the size required to code for the specific protein for which it is a template, often by a factor of 2 or 3. The extra nucleotides occur in untranslated (non-protein coding) regions both 5' and 3' of the coding region; the longest untranslated sequences are usually at the 3' end. The exact function of these sequences is unknown, but they have been implicated in RNA processing, transport, degradation, and translation; each of these reactions potentially contributes additional levels of control of gene expression.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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