Mechanisms for mRNA Degradation

The small ribosomal subunit, amongst other things, is initiates the engagement of the mRNA and is responsible decoding the genetic information during translation [4].

Enzymes combine with reactant molecules (substrate) and bind them closely to one another. The three-dimensional shape of the enzyme molecule must be complementary to the shape of the substrate.

After reviewing the basics of enzymes and catalysis, we take a dive into the wonderful

Genes expression is what encodes many proteins to give function to a cell. It involves many steps that mostly include transcription and translation. Transcription alone does not play a role in gene expression (Erster Lect. 24). There are many post-transcriptional regulatory mechanisms that have been found to be involved. These mechanisms are a part of RNA processing. One of this can occur through alternative splicing. This is when exons of the same gene are spliced together to produce different mRNA molecules (Reece, et al. 372). Regulating gene expression also occurs during translation. mRNA lifespan within the cytoplasm is significant when it comes to determining the arrangement of protein synthesis. These mRNA molecules tend to be degraded by enzymes moments

enable the substrate to bind to the enzyme and form the enzyme substrate complex and

Enzymes are proteins that act as a catalyst in bringing about specific biochemical reactions when met with particular substrates. Substrates will merge into a suitable area of the enzyme called an active site – this becomes the enzyme/substrate complex. Once the substrate is attached to the active site, the substrate will undergo a procedure where the substrate is modified and released as a product. There are different types of this that can occur, where either a chemical bond is broken in a substrate to produce two separate products; as in the ‘Induced-Fit’ model illustrated in figure 1.a. Chemical bonds can also be built between two substrates to produce a single product.

protein and it deletes a small amount of DNA from the CFTR gene. I am going to explain what

18. What contribution from the intrinsic and the extrinsic pathways is necessary for the common pathway to begin?

Corporation, W. B. (2013). Introduction to Enzymes. Retrieved 2013 йил 27-2 from Worthington Biochemical Corporation: https://gateway.emmanuel.qld.edu.au/cvpn/aHR0cDovL3d3dy53b3J0aGluZ3Rvbi1iaW9jaGVtLmNvbQ/introbiochem/effectsph.html

(Except that uracil replaces thymine). The nucleotides form sugar-phosphate bonds with each other and become an mRNA strand but they do not form bonds with the DNA strand. The sequence of three exposed bases on mRNA, that are complimentary to the base triplet on the DNA, are known as codons. Once the mRNA strand is complete it moves from the DNA in the nucleus, through the nuclearpore into the cytoplasm where it drapes itself over the ribosomes with their codons exposed. Floating in the cytoplasm are tRNA molecules which job is to pick up specific amino acids and transport them to where the mRNA is draped.

It took an additional six years for researchers to glimpse at the functions provided by SMN1. Meister et al. categorized the SMN1 protein an essential to promote correct assembly of U12 small ribonucleoproteins (snRNPs). In genetics, snRNPs are nucleic proteins responsible for the splicing of premature ribonucleic acid chains (pre-mRNA) derived from genes. Without correct splicing, mature ribonucleic acid chains (mRNAs) produce dysfunctional proteins when translated. In this case, splicing functionality of U12 - intron containing transcripts is lost, and because the transcript is wrongly coded, its translation will produce a functionless protein. Hence, loss of SMN1 results in an inability form U12 snRNPs splicing complexes, and reduced splicing functionality results in loss of U12 - intron splicing functionality (Patel and Steitz, 2003).

There are six main types of enzyme reactions which include oxidation/reduction, group transfer, hydrolysis, formation or removal of double bond, isomerization of functional

Before leaving the nucleus the pre-mRNA may go through a process called RNA splicing (Brooker). During this process the undesirable introns are disposed of while the coding sequences, exons, are spliced together to form messenger RNA (Brooker). Understanding RNA splicing, the most important process that may alter a protein’s shape is alternative splicing (Brooker). This process allows one strand of pre-messenger RNA to produce several different polypeptide sequences (Brooker). One pre-mRNA can create multiple polypeptide sequences which in turn creates proteins that are distinctive from each other. Alternative splicing is seen in the LMNA gene, it produces Lamins A and C (Swahari). Although they are different proteins, they are believed to be functionally redundant (Swahari). During the formation of these proteins a farnesyl group, which embeds into the cell membrane, is added to one end and later the protein is cleaved at a recognition site in exon 11 removing the tip and the farnesyl group (Swahari). Due to the point mutation linked to HGPS 50 amino acids are removed, within these is the recognition site (Swahari). As a result the protein is permanently farnesylated and known as progerin (Swahari). This protein imbeds and accumulates in the cell membrane creating the symptoms of HGPS (Swahari).

ways. Each enzyme has specific ranges at which it optimally functions; in general, increasing the

Briefly, cells will be treated with cyclohexamide to arrest translating ribosomes. Extracts from these cells will be treated with RNase I to degrade regions of mRNAs not protected by ribosomes. The resulting 80S monosomes, which contain a ∼30-nucleotide RPF, will be purified on sucrose gradients and then treated to release the RPFs, which are then processed for Illumina high-throughput sequencing. In parallel, poly (A)-selected mRNA from each sample was randomly fragmented, and the resulting mRNA fragments will be processed for sequencing (mRNA-Seq) using the same protocol as that used for the RPFs. In summary, these experiments will pinpoint the targets, which are translated in UPF1 mutant cells.