Pre-mRNA

The ACHE gene includes sites for alternative splicing of its pre-mRNA product both at the 5 and the 3 ends. Three different carboxy termini exist the synaptic or S variant also called as tailed , the erythrocytic or E variant and the readthrough or R variant. These join the two different N-termini to yield variants with the common or the extended N-terminus. 

Interestingly, the genomic sequences of all AMPA receptor subunits contain a Q codon for this position and the R codon is selectively introduced into the GluR-B pre-mRNA by RNA editing [3]. Additionally, the Q/R site is a critical determinant of current... 

Splicing is a processing step of the pre-mRNA to become a mature transcript. This involves the excision of intervening noncoding sequences (introns) from coding sequences (exons) by a multiple protein complex, the spliceosome. After splicing the mRNA molecule is ready for translation, since it contains a continuous sequence that encode an entire protein. 

Karras J.G., Maier M.A., Lu T, Watt A., Manoharan M. Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine inter-leukin-5 receptor-alpha chain. Biochemistry 2001 40 7853-7859. 

Eukaryotic mRNA synthesis results in a pre-mRNA precursor that contains extensive amounts of excess RNA (introns) that must be precisely removed by RNA splicing to generate functional, translatable mRNA composed of exonic coding and noncoding sequences. 

C9. Cheng, J., and Maquat, L. E., Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA. Mol. Cell. Biol. 13,1892-1902 (1993). 

Sarmah, B., Chakraborty, N., Chakraborty, S. and Datta, A. (2002) Plant pre-mRNA splicing in fission yeast, Schizosaccharomyces pombe. Biochemical and Biophysical Research Communications, 293 (4), 1209—1216. 

Izaurralde, E., Lewis, J., McGuigan, C., Jankowska, M., Darzynkiewicz, E., and Mattaj, I. W. (1994). A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78, 657-668. 

Eukaryotes have a specific signal for termination of transcription however, prokaryotes seem to have lost this mechanism. Once started, RNA polymerase keeps going, making a primary transcript [pre-mRNA or hnRNA (for heterogeneous nuclear)] until far past the end of the final mRNA message. 

Pellizzoni, L., Kataoka, N., Charroux, B. and Dreyfuss, G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell 95 615-624, 1998. 

Ishikawa F, Matunis MJ, Dreyfuss G, Cech TR (1993) Nuclear proteins diat bind die pre-mRNA 3 splice site sequence r(UUAG/G) and die human telomeric DNA sequence d(TTAGGG)n. Mol Cell... 

Zeitlin S, Parent A, Silverstein S, Efstratiadis A (1987) Pre-mRNA splicing and the nuclear matrix. Mol Cell Biol 7(1) 111-120... 

Heterogeneous nuclear RNA (huRNA or pre-mRNA), which is found only in the nucleus of eukaryotic cells. It represents precursors of mRNA, formed during its post-transcriptional processing. 

Posttranscrip-tional processing of hnRNA (pre-mRNA) None In nucleus 5 cap (7-MeG) 3 tail (poly-A sequence) Removal of introns from hnRNA Alternative splicing yields variants of protein product... 

Answer A. Polyadenylation of pre-mRNA occurs in the nucleoplasm. Generally associ-... 

Those RNA molecules destined to function as mRNA are chemically modified following transcription. The immediate product of transcription is termed pre-mRNA. There are two classes of these modifications that lead to mature, functional mRNA alteration of the mRNA ends and spUcing. 

Just as pre-mRNA molecules are chemically modified to create functional mRNA (figure 13.2), nascent proteins may be chemically modified to create fully functional molecules. There are two general mechanisms at work here proteolytic cleavage and covalent modification. 

Spliceosome a protein complex that catalyzes the splicing out of introns in pre-mRNA. 

Figure 20.20 Summary of transcription, RNA processing and polypeptide synthesis. Polymerisation of the DNA template by RNA polymerase produces pre-mRNA (the primary transcript) this is transcription. The pre-mRNA is now processed, which involves capping, polyadenylation, editing and splicing (see text). The resultant mRNA transfers from the nucleus to the cytosol, where amino acids are polymerised to produce a polypeptide using the instructions present in the codons of the mRNA.

RNA editing This process involves insertion, deletion or modification of nucleotides in the pre-mRNA. The result of one or more of these modifications is that the mRNA is sufficiently modified fhat the properties of the proteins that are produced are slightly different in different tissues. A cytidine base can be converted to uracil in mRNA in a reaction catalysed by a deaminase enzyme. This can result... 

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