Messenger RNA splicing

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All eukaryotic cells have four major classes of RNA ri-bosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). The first three are involved in protein synthesis, and snRNA is involved in mRNA splicing. As shown in Table 37-1, these various classes of RNA are different in their diversity, stability, and abundance in cells. 

Fig. 24.4 Splicing of a messenger RNA molecule transcribed from a hypothetical insulin gene containing two introns.

Ichinose, H., Sumi-Ichinose, C., Ohye, T., Hagino, Y., Fujita, K., and Nagatsu, T. (1992). Tissue-specific alternative splicing of the 1st exon generates 2 types of messenger-RNAs in human aromatic L-amino acid decarboxylase. Biochemistry 31 11546— 11550. 

Transcript discovery Find transcripts (genes) in genomic sequence In these experiments, arrays are made from genomic DNA sequences, rather than from complementary DNAs (cDNAs). Such studies can be used to confirm computational gene predictions and characterize alternative splicing and die boundaries of exons (DNA sequences destined to become part of die mature messenger RNA [mRNA]). 

The various ways in which messenger RNA molecules may be spliced provides a mechanism for diversity in protein structures derived from a single gene. 

The removal of introns from pre-messenger RNAs in eukaryotes is catalyzed by the spliceosome, which is a large ribonucleoprotein consisting of at least 70 proteins and five small nuclear RNAs (snRNA) [144]. This splicing pathway involves two phosphotransfer reactions. In the first step, the 5 splice site is attacked by a 2 hydroxy group of an adenosine nucleotide within the intron [indicated by A in Fig. 12] that corresponds to the branch point in the lariat intermediate (Fig. 12,middle). In the second step, the 3 -OH group of the free 5 exon attacks the phosphodiester bond between the intron and... 

Nearly all of the RNA of the cell is synthesized (transcribed) in the nucleus, according to the instructions encoded in the DNA. Some of the RNA then moves out of the nucleus into the cytoplasm where it functions in protein synthesis and in some other ways. Many eukaryotic genes consist of several sequences that may be separated in the DNA of a chromosome by intervening sequences of hundreds or thousands of base pairs. The long RNA transcripts made from these split genes must be cut and spliced in the nucleus to form the correct messenger RNA molecules which are then sent out to the ribosomes in the cytoplasm. 

Factor IX (Christmas factor) is next in the intrinsic mechanism cascade. It can be activated either by XIa or by Vila of the tissue factor pathway. The absence of a functional factor IX leads to the inherited X-linked bleeding disorder hemophilia B which affects 1 in 30,000 males. The condition can be mild or very serious551552 and may be caused by a variety of mutations or by incorrect splicing of the messenger RNA for the 416-residue factor IX. The level of factor IX in blood increases with age, almost doubling by old age.552a... 

Berthele, A., Laurie, D. J., Platzer, S., Zieglgansberger, W., Tolle, T. R., and Sommer, B. (1998). Differential expression of rat and human type I metabotropic glutamate receptor splice variant messenger RNAs. Neuroscience 85, 733-749. 

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