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Biochemistry

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Purines, Pyrimidines and Nucleic Acid Metabolism

Question
18 out of 59
 

Poly A tail translates into (AIIMS Nov 2010)



A Polylysine
B Polyproline

C Polyalanine
D Polyglycine

Ans. A Polylysine

Ref: Harper Illustrated Biochemistry 28Ed ch 37

1. Eukaryotic mRNA

a. The RNA molecule synthesized by RNA polymerase II (the primary transcript) contains the sequences that are found in cytosolic mRNA. The collection of all the precursor molecules for mRNA is known as heterogeneous nuclear RNA (hnRNA). The primary transcripts are extensively modified in the nucleus after transcription.

b. These modifications usually include:

i. 5’ “Capping”: This process is the first of the processing reactions for hnRNA. The cap is a 7-methylguanosine attached “backward” to the 5’-terminal end of the mRNA, forming an unusual 5’ 5’ triphosphate linkage. The creation of the guanosine triphosphate part of the cap requires the nuclear enzyme guanylyltransferase. Methylation of this terminal guanine occurs in the cytosol, and is catalyzed by guanine-7-methyltransferase. S-adenosylmethionine is the source of the methyl group. Additional methylation steps may occur. The addition of this 7-methylguanosine “cap” permits the initiation of translation, and helps stabilize the mRNA. Eukaryotic mRNA lacking the cap are not efficiently translated.

ii. Addition of a poly-A tail: Most eukaryotic mRNA (with several notable exceptions, including those coding for the histones and some interferons) have a chain of 40–200 adenine nucleotides attached to the 3’-end. This poly-A tail is not transcribed from the DNA, but rather is added after transcription by the nuclear enzyme, polyadenylate polymerase, using ATP as the substrate. The mRNA is cleaved downstream of a consensus sequence, called the polyadenylation signal sequence (AAUAAA), found near the 3’-end of the RNA, and the poly-A tail is added to the new 3’-end. These tails help stabilize the mRNA and facilitate their exit from the nucleus. After the mRNA enters the cytosol, the poly-A tail is gradually shortened. the poly-A tail is translated to polylysine

iii. Removal of introns:

a. Maturation of eukaryotic mRNA usually involves the removal of RNA sequences, which do not code for protein (introns, or intervening sequences) from the primary transcript. The remaining coding sequences, the exons, are joined together to form the mature mRNA.

b. The process of removing introns and joining exons is called splicing. The molecular machine that accomplishes these tasks is known as the spliceosome. A few eukaryotic primary transcripts contain no introns, for example, those from histone genes.

c. Others contain a few introns, whereas some, such as the primary transcripts for the α chains of collagen, contain more than fifty intervening sequences that must be removed before mature mRNA is ready for translation.

2. Role of snRNAs:

a. In association with proteins, snRNA form small nuclear ribonucleoprotein particles (snRNP, or “snurps”) that mediate splicing. They facilitate the removal of exon segments by forming base pairs with the consensus sequences at each end of the intron.

b. Mechanism of splicing: The binding of snRNP brings the sequences of the neighboring exons into the correct alignment for splicing. The 2’-OH group of an adenosine (A) residue (known as the branch site) in the intron attacks the phosphate at the 5’-end of the intron, forming an unusual 2’5’ phosphodiester bond and creating a “lariat” structure. The newly freed 3’-OH of exon 1 attacks the 5’-phosphate at the splice acceptor site, forming a phosphodiester bond that joins exons 1 and 2. The excised intron is released as a lariat, which is degraded.

c. [Note: The GU and AG sequences at the start and end, respectively, of introns are invariant.] After introns have been removed and exons joined, the mature mRNA molecules leave the nucleus and pass into the cytosol through pores in the nuclear membrane.

d. [Note: The introns in tRNA are removed by a mechanism different than splicing.]

e. Effect of splice site mutations: Mutations at splice sites can lead to improper splicing and the production of aberrant proteins. It is estimated that fifteen percent of all genetic diseases are a result of mutations that affect RNA splicing.

f. For example, mutations that cause the incorrect splicing of β-globin mRNA are responsible for some cases of β-thalassemia—a disease in which the production of the β-globin protein is defective.

3. Alternative splicing of mRNA molecules:

a. The pre-mRNA molecules from some genes can be spliced in two or more alternative ways in different tissues. This produces multiple variations of the mRNA and, therefore, of its protein product.

b. This appears to be a mechanism for producing a diverse set of proteins from a limited set of genes.

c. For example, different types of muscle cells all produce the same primary transcript from the tropomyosin gene. However, different patterns of splicing in the different cell types produce a family of tissue-specific tropomyosin protein molecules

Purines, Pyrimidines and Nucleic Acid Metabolism Flashcard List

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