Thursday, 8 September 2011

Structure of a Telomerase RNA

RNA is transcribed with only four bases (adenine, cytosine, guanine and uracil), but there are numerous modified bases and sugars in mature RNA's. Pseudouridine (Ψ) in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond and ribothymidine (T) are found in various places (most notably in the TΨC loop of tRNA). Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine (I). Inosine plays a key role in the wobble hypothesis of the genetic code. There are nearly 100 other naturally occurring modified nucleosides, of which pseudouridine and nucleosides with 2'-O-methylribose are the most common. The specific roles of many of these modifications in RNA are not fully understood. However it is notable that in ribosomal RNA many of the post-transcriptional modifications occur in highly functional regions, such as the peptidyl transferase center and the subunit interface implying that they are important for normal function

The functional form of single stranded RNA molecules, just like proteins, frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements which are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like hairpin loops, bulges and internal loops. Since RNA is charged, metal ions such as Mg2+ are needed to stabilize many secondary and tertiary structures.

DNA repair Mechanisms

Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the genome (but cells remain superficially functional when so-called "non-essential" genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister chromatid as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as translation synthesis as a last resort

Damage to DNA alters the spatial configuration of the helix and such alterations can be detected by the cell. Once damage is localized, specific DNA repair molecules bind at or near the site of damage, inducing other molecules to bind and form a complex that enables the actual repair to take place. The types of molecules involved and the mechanism of repair that is mobilized depend on the type of damage that has occurred and the phase of the cell cycle that the cell is in Dna.

DNA and RNA

There are actually 2 main types of nucleic substances within cell nuclei that process information. DNA is the basic form within chromosomes that is hard-coded into every cell. RNA is a more temporary form that is used to process subsequences of DNA messages. RNA is an intermediate form used to execute the portions of DNA that a cell is using. For example, in the synthesis of proteins, DNA is copied to RNA, which is then used to create proteins: DNA->RNA->Proteins. The structure of DNA and RNA are very similar. They are both ordered sequences of 4 types of substances: ACGT for DNA and ACGU for RNA. Thus RNA uses the same three ACG substances, but uses U (uracil) instead of T (thymine). The molecules uracil and thymine are only slightly different chemically. In DNA, there is pairing between AT and CG, and in RNA, the pairings are AU and CG, but since RNA is not double-stranded, this pairing is much rarer. Hence, RNA has the 4 substances:-
  1. A: Adenosine
  2. C: Cytosine
  3. G: Guanine
  4. U: Uracil
Typically, DNA is created from RNA, and this is done by faithfully copying the sequence of base pairs, with the only change converting T to U. Hence, an RNA copy of a DNA sequence encodes the identical information, though it uses a slightly different set of 4 substances. The differences between DNA and RNA are also many. The underlying sugar molecule that traps the 4 bases is different: deoxyribose in DNA, ribose in RNA. DNA is two strands wrapped in a double-helix, but RNA is a single strand.

Sequences in DNA

Proteins are not the only substances that are synthesized directly from data within the DNA. Some forms of RNA are specialized, and also have their formula encoded directly in digital DNA formulae. Not all types of RNA are temporary intermediate forms with their form depending on whatever DNA they are copying. There are certain forms of RNA that have a particular form that is the same across all individuals. Some of these special-purpose RNA forms are
  • tRNA: transfer RNA
  • rRNA: ribosome RNA
There are exactly 20 forms of tRNA, one each to transfer a particular amino acid. tRNA molecules contain about 75-80 bases. tRNA recognizes one of the 64 triplets, and matches it to one of the 20 amino acids. Since there are 20 tRNA types, and not 64, each tRNA molecule has to recognize more than one triplet ordering as a match. The DNA code contains multiple repetitions of the codes for tRNA and rRNA. About 280 copies are spread over 5 chromosomes. Presumably, this allows each cell to make multiple copies of tRNA and rRNA molecules at once from its single copy of the DNA.

Computational Evolution in Biology

Bioinformatics was applied in the creation and maintenance of a database to store biological information at the beginning of the "genomic revolution", such as nucleotide and amino acid sequences. Development of this type of database involved not only design issues but the development of complex interfaces whereby researchers could both access existing data as well as submit new or revised data.In order to study how normal cellular activities are altered in different disease states, the biological data must be combined to form a comprehensive picture of these activities. Therefore, the field of bioinformatics has evolved such that the most pressing task now involves the analysis and interpretation of various types of data, including nucleotide and amino acid sequences, protein domains, and protein structures. The actual process of analyzing and interpreting data is referred to as computational biology

Important sub-disciplines within bioinformatics and computational biology include

1. the development and implementation of tools that enable efficient access to, and use and management of, various types of information

2. the development of new algorithms and statistics with which to assess relationships among members of large data sets, such as methods to locate a gene within a sequence, predict protein structure and/or function, and cluster protein sequences into families of related sequences.