RNA-Ribonucleic Acids

Ribonucleic acid, or RNA, is a nucleic acid very similar to DNA. Its structure is the same, although it is usually found single-stranded instead of double stranded like DNA. In place of deoxyribose, RNA has ribose, and in place of the base thymine, RNA has uracil. But with all these structural similarities to DNA, the function can’t differ too much either, right? That assumption couldn’t be more wrong.

What is RNA?

While DNA is meant to provide the genetic information used in heredity and as the blueprints for building all the proteins in the human body, RNA’s jobs vary from simple carriers of building blocks to interpreting some of the most important information in the human body. In its many forms, RNA is responsible for forming ribosomes, the structures used to assemble protein strings, carrying amino acids in and out of their ‘storage’ in the cytoplasm, and carrying a copy of the genetic information housed in the DNA to ribosomes for protein creation. As we shall see, each type of RNA has special structural qualities that make it suited for its own specific function. But first we must learn what RNA is in general and why it is considered the bridge between DNA and proteins.

The steps RNA takes to achieve its ultimate goal of creating protein molecules falls under one of two major tasks: transcription and translation. Transcription describes the process by which an RNA strand is synthesized from a section of DNA called the transcription unit. Translation occurs when all the types of RNA, each in a different role, come together to assemble a protein molecule. Because bacteria lack a nucleus to separate structures, bacteria RNA starts being translated before it is finished being transcribed. But in eukaryotes the creation of proteins is more complicated and therefore takes more steps. The language of the information RNA carries between DNA and proteins is in a triplet code. To find out why the information in RNA comes packaged in triplets, one must look no further than what RNA has to work with and what it is trying to do. RNA must be able to code for the 20 amino acids humans need to survive, and they have 4 bases to do it. Why not use two bases at a time? That would only provide for 4 2 (16) amino acids. But if RNA information is grouped in non-overlapping codons, or three letter groups each standing for an amino acid, then the RNA code can represent 43 (64) amino acids, more than enough to sustain human life.

RNA transcription

The three stages in RNA transcription are initiation, elongation, and termination. The first stage, initiation, begins with what is called the transcription initiation complex. This complex consists of RNA polymerase, an enzyme that separates the two DNA strands and attaches to the one it is going to copy (the DNA template strand). It is also used to elongate the DNA template strand in the 5’ to 3’ direction. The other part of the transcription initiation complex is a collection of proteins called transcription factors which, in eukaryotes, find the location on the DNA template strand where RNA polymerase is going to attach itself (this location is called the promoter region). One of the most important promoters is called the TATA box; it is the DNA sequence where the template strand unwinds from the other strand. As RNA polymerase unwinds the DNA strands over the area it is going to copy, called the transcription unit, only a few base pairs are exposed at a time. About 10-20 base pairs are exposed to be copied to the 3’ end of the new RNA strand. Once polymerase hits a special region called the terminator region, the transcription process stops. When this entire process is completed, the RNA molecule is now a separate, single-stranded string of genetic data able to leave the cell nucleus to carry out its different functions.

One type of RNA created is called messenger RNA, or mRNA. The function of mRNA is to direct the synthesis of a polypeptide chain, or the creation of a protein. In eukaryotes, the translation of mRNA comes in two steps: the first makes a pre-mRNA strand, and the second step processes the molecule to make a final mRNA strand. The pre-mRNA is called the initial transcript and is eventually altered to allow it leave the nucleus and stay intact when it does. During processing, the 5’ end of the mRNA is immediately capped with a modified guanine nucleotide meant to protect the mRNA strand from degradation by hydrolytic enzymes outside of the nucleus. This guanine cap is also used as a way to signal a ribosome to attach to the mRNA at the G-cap. At the 3’ end the pre-mRNA strands get a poly(A) tail, 30 to 200 nucleotides long, meant to help with degradation and ribosome attachment but also helps it to pass through the nuclear membrane. Although these modifications are important to the function of mRNA, one even more important modification must occur before the mRNA strand is ready to direct protein production.

The average length of a transcription unit in eukaryote DNA is 8000 nucleotides long. However, with the average protein size at about 400 amino acids (meaning 400 * 3, or 1200 nucleotides), there appears to be a large portion of wasted RNA information. A process called RNA splicing is used to cut out the non-encoding regions of RNA and to piece back together the remaining expressed regions. The non-encoding regions are called intervening sequences, or introns, while the other regions are called expressed regions, or exons. In to know which regions need to be cut, introns have special nucleotide sequences at their ends that are recognized by small nuclear ribonucleoproteins, or snRNP’s, which are in the cell nucleus and are made of RNA and proteins. The RNA in snRNP’s are called small nuclear RNA, or snRNA, and are about 150 nucleotides long. Multiple snRNP’s join together with specific proteins to form a unit called a spliceosome. This structure is designed to cut at the points on an RNA strand to release the introns and then recombine the exons to make one continuous RNA strand. Evidence strongly suggests that the snRNA in a spliceosome is a ribozyme (an RNA molecule that acts as a catalyst) and speeds up the cutting and pasting process. With the introns cut out and exons spliced back together, there is now a fully functional mRNA molecule ready to create proteins.

Transfer RNA: The cell’s brick layer

Another type of RNA used in protein synthesis is the transfer RNA, or tRNA. This nucleic acid is used to transfer amino acids from its storage in the cytoplasm to the ribosome for protein synthesis. The tRNA also links an mRNA codon with its corresponding amino acid by an enzyme called aminoacyl-tRNA synthetase. The physical structure of tRNA could not be more important to these tasks. A tRNA strand is about 80 nucleotides long and folds back on itself to create a 3 dimensional structure.

Click to enlarge. The structure of tRNA.(From embnet)

At one end of this structure is an unpaired triplet of bases called the anticodon, which is meant to bind to the codon of an mRNA. At the other end of tRNA is an amino acid attachment site to recognize the specific acid called for by the mRNA to make a protein. If there were one tRNA for each mRNA codon that called for an amino acid, there would be 60 tRNA types. However, there are actually only about 45. The reason for this is the versatility of some of the bases. For example uracil, the substitution for thymine in RNA, can attach to adenine or guanine if it’s in the third position of the anticodon. Inosine, a base modified by an ebzymatic alteration of adenine after the tRNA is synthesized, can bond with uracil, cytosine, or adenine. This exception to the normally strict base-pairing rule is called wobble.

Click to enlarge. The structure of tRNA.(Transfer RNA, n.d.)

 

Putting it all together in ribosomal RNA

Ribosomal RNA, or rRNA, together with various proteins makes up the ribosomes. Ribosomes are needed to convert mRNA information into polypeptide strings. The ribosome is actually made up of two subunits, the small subunit and the large subunit, which only come together when converting mRNA information to amino acids. rRNA is the biggest part of ribosomes, being almost 60% of a ribosome’s weight. Because of the thousands of ribosomes each cell has, rRNA is the most abundant form of RNA in the human body. This rRNA is synthesized in a specialized structure within the nucleus called the nucleolus. Once combined to form the ribosome, it interacts with tRNA and mRNA at three different regions called sites. The P site (peptidyl-tRNA site) holds the newly forming polypeptide chain attached to a tRNA molecule. The A site(aminoacyl-tRNA site) holds the amino acid about to be added to the chain and its carrier tRNA molecule. Once done with its job at a ribosome, a tRNA molecule exits by means of the E site (exit site). While adding to the growing polypeptide chain, a ribosome holds the mRNA and tRNA together in a firm grip so the amino acids can be added correctly.

Click to englarge. Ribosome translating a tRNA strand into a protein.

 

It is through these three types of RNA that a bridge can be formed between the information coded on helices of DNA safeguarded in the nucleus and the active protein molecules built from that information. By using a similar base-pairing system, RNA ensures that any protein molecules created by the ribosome follow the strict instructions coded by the DNA strands. mRNA gives the instructions for protein building, tRNA provides the amino acids to make the proteins, and rRNA gives the means for creating such elaborate strings as proteins. Thanks to RNA, a cell can keep its core information safe while making the most of the information it has.

References

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