40

2.4  Cell Processes

6 In the case of eukaryotic cells, the mRNA molecule first diffuses out of the nucleus

through specialized nanoscale holes in the nuclear membrane called “nucleopores”

and can then be modified by enzyme-​medicated splicing reactions called

posttranscriptional modifications that can result in significant variability from the ori­

ginal mRNA molecule manifested as sequence differences in the proteins or peptides

that are ultimately generated. Each eukaryotic gene, in general, consists of coding

DNA regions called “exons” interspersed with noncoding regions called “introns,”

and splicing of the mRNA involves in effect differential shuffling and relinking of the

equivalent exon regions in the mRNA by a complex molecular machine called the

“spliceosome.” In prokaryotes, there are no introns and no established mechanisms

for posttranscriptional modifications.

7 The mRNA molecule, whether modified or not, ultimately then binds to a ribo­

some in the cytoplasm. Ribosomes are structures roughly 20 nm in average diam­

eter, composed of a mixture of RNA called “rRNA” and proteins. Once bound to a

ribosome, the mRNA molecule is translated into a peptide, or protein, sequence, at

a typical rate of 8 amino acids per second in eukaryotes, and more likely twice this in

prokaryotes.

The mRNA is actually read off in chunks of three consecutive bases, called a “codon.”

In principle, this equates to 4³, or 64, possible combinations; however, since there are only

20 natural amino acids, there is degeneracy, in that multiple codons may code for the same

amino acids (typically between two and six codons exist per amino acid mainly by variation

in the third base pair, but two amino acids of methionine in eukaryotes, or formylmethionine

in bacteria, and tryptophan are specified by just a single codon). The mRNA sequence for

methionine/​formylmethionine is denoted AUG, since it consists of adenine, uracil, and

guanine, and is a special case since it acts as the start codon in most organisms. Similarly,

there are also stop codons (UAA, UAG, and UGA), which consist of other combinations of

these three nucleotide bases, also called “nonsense codons or termination codons,” which do

not code for an amino acid but terminate mRNA translation. The region between the start

and the nearest upstream stop codon is called the “open reading frame,” which generally, but

not always, codes for a protein, and in which case is called a “gene.”

Each tRNA molecule acts as an adapter, in that there is a specific tRNA that is attached

to each a specific amino acid (Figure 2.7b). Each tRNA molecule then binds via an anticodon

binding site to the appropriate codon on the mRNA bound to a ribosome (Figure 2.7c). The

general structure of the ribosome consists of a large and small subunit stabilized by base

pairing between rRNA nucleotides, which assembles onto the start sequence of each mRNA

molecule, sandwiching it together.

The sandwich acts as the site of translation, such that tRNA molecules bind transiently

to each active codon and fuse their attached amino acid residues with the nearest upstream

amino acid coded by the previous mRNA codon, with the site of active translation on the

mRNA shunted forward by moving the mRNA molecule through the ribosome by another

codon unit in a process that is energized by the hydrolysis of the molecule GTP (similar to

ATP). Multiple ribosomes may bind to the same mRNA molecule to form a polysome (also

known as a polyribosome) cluster that can manufacture copies of the same protein from just

a single mRNA template each individual ribosome outputting proteins in parallel.

2.4.2  DETECTION OF SIGNALS

Cells can detect the presence of external chemicals with remarkable specificity and efficiency.

The typical way this is achieved is through a highly specific receptor that is integrated into the

cell membrane composed mainly of protein subunits. The unique 3D spatial conformation

adopted by the receptor can allow specific binding of a ligand molecule if it has a conform­

ation that can efficiently fit into the 3D binding site of the receptor; biologists sometimes

describe this as a lock-​and-​key mechanism and is also the way that enzymes are believed to