Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Ribonucleic acid (RNA)

489

•

Thinking it was a phosphorus-rich nuclear protein, Miescher

named it nuclein.

The substance identified by Miescher was actually a pro-

tein plus nucleic acid, as the German biochemist Albrecht

Kossel discovered in the 1880s. Kossel also isolated nucleic

acids’ two purines (adenine and guanine) and three pyrimidines

(thymine, cytosine, and uracil), as well as carbohydrates.

The American biochemist Phoebus Levene, who had

once studied with Kossel, identified two nucleic acid sugars.

Levene identified ribose in 1909 and deoxyribose (a molecule

with less oxygen than ribose) in 1929. Levene also defined a

nucleic acid’s main unit as a phosphate-base-sugar nucleotide.

The nucleotides’ exact connection into a linear polymer chain

was discovered in the 1940s by the British organic chemist

Alexander Todd.

In 1951, American molecular biologist James Watson

and the British molecular biologists Francis Crickand Maurice

Wilkins developed a model of DNA that proposed its now

accepted two-stranded helical shape in which adenine is

always paired with thymine and guanine is always paired with

the cytosine. In RNA, uracil replaces thymine.

During the 1960s, scientists discovered that three con-

secutive DNA or RNA bases (a codon) comprise the genetic

codeor instruction for production of a protein. Ageneis tran-

scribed into messenger RNA (mRNA), which moves from the

nucleusto structures in the cytoplasm called ribosomes.

Codons on the mRNA order the insertion of a specific amino

acid into the chain of amino acids that are part of every pro-

tein. Codons can also order the translationprocess to stop.

Transfer RNA (tRNA) molecules already in the cytoplasm

read the codon instructions and bring the required amino acids

to a ribosome for assembly.

Some proteins carry out cell functions while others con-

trol the operation of other genes. Until the 1970s cellular RNA

was thought to be only a passive carrier of DNA instructions.

It is now known to perform several enzymatic functions

within cells, including transcribing DNA into messenger RNA

and making protein. In certain virusescalled retroviruses,

RNA itself is the genetic information. This, and the increasing

knowledge of RNA’s dynamic role in DNA cells, has led some

scientists to argue that RNA was the basis for Earth’s earliest

life forms, an environment termed the RNA World.

The first step in protein synthesis is the transcriptionof

DNA into mRNA. The mRNA exits the nuclear membrane

through special pores and enters the cytoplasm. It then deliv-

ers its coded message to tiny protein factories called ribo-

somes that consist of two unequal sized subunits. Some of

these ribosomes are found floating free in the cytosol, but

most of them are located on a structure called rough endo-

plasmic reticulum (rER). It is thought that the free-floating

ribosomes manufacture proteins for use within the cell (cell

proliferation), while those found on the rER produce proteins

for export out of the cell or those that are associated with the

cell membrane.

Genes transcribe their encoded sequences as a RNA

template that plays the role of precursor for messenger RNA

(mRNA), being thus termed pre-mRNA. Messenger RNA is

formed through the splicing of exons from pre-mRNA into a

sequence of codons, ready for protein translation. Therefore,

mRNA is also termed mature mRNA, because it can be trans-

ported to the cytoplasm, where protein translation will take

place in the ribosomal complex.

Transcription occurs in the nucleus, through the follow-

ing sequence of the events. The process of gene transcription

into mRNA in the nucleus begins with the original DNA

nitrogenous base sequence represented in the direction of tran-

scription (e.g. from the 5’ [five prime] end to the 3’ [three

prime] end) as DNA 5’...AGG TCC TAG TAA...3’ to the for-

mation of pre-mRNA (for the exemplar DNA cited) with a

sequence of 3’...TCC AGG ATC ATT...5’ (exons transcribed to

pre-mRNA template) then into a mRNA sequence of 5’...AGG

UCC UAG UAA...3’ (codons spliced into mature mRNA).

Messenger RNA is first synthesized by genes as nuclear

heterogeneous RNA (hnRNA), being so called because

hnRNAs varies enormously in their molecular weight as well

as in their nucleotide sequences and lengths, which reflects the

different proteins they are destined to code for translation.

Most hnRNAs of eukaryotic cells are very big, up to 50,000

nucleotides, and display a poly-A tail that confers stability to

the molecule. These molecules have a brief existance, being

processed during transcription into pre-mRNA and then in

mRNA through splicing.

The molecular weight of mRNAs also varies in accor-

dance with the protein size they encode for during translation.

Because three nucleotides are needed for the translation of

each amino acid that will constitute the polypeptide chain dur-

ing protein synthesis, they necessarily are much bigger than

the protein itself. Prokaryotic mRNA molecules usually have

a short existence of about 2–3 minutes, but the fast bacterial

mRNA turnover allows for a quick response to environmental

changes by these unicellular organisms. In mammals, the aver-

age life span of mRNA goes from 10 minutes up to two days.

Therefore, eukaryotic cells in mammals have different mole-

cules of mRNA that show a wide range of different degrada-

tion rates. For instance, mRNA of regulatory proteins,

involved either in cell metabolismor in the cell cyclecontrol,

generally has a short life of a few minutes, whereas mRNA for

globin has a half-life of 10 hours.

The enzyme RNA-polymerase II is the transcriptional

element in human eukaryotic cells that synthesizes messenger

RNA. The general chemical structure of most eukaryotic

mRNA molecules contain a 7-methylguanosine group linked

through a triphosphate to the 5’ extremity, forming a cap. At

the other end (i.e., 3’ end), there is usually a tail of up to 150

adenylils or poly-A. One exception is the histone mRNA that

does not have a poly-A tail. It was also observed the existence

of a correlation between the length of the poly-A tail and the

half-life of a given mRNA molecule.

At the biochemical level, RNA molecules are linear

polymers that share a common basic structure comprised of a

backbone formed by an alternating polymer of phosphate

groups and ribose (a sugar containing five carbon atoms).

Organic nitrogenous bases i.e., the purines adenine and gua-

nine, and the pyrimidines cytosine and uracil are linked

together through phosphodiester bridges. These four nitroge-

nous bases are also termed heterocyclic bases and each of

womi_R 5/7/03 8:17 AM Page 489