9. Central Dogma -- Part II (744)

Once an mRNA has been processed, it's packaged with proteins and transported through nuclear pores--large channels in the nuclear membrane--into the cytoplasm, where it can be translated into protein.

The central player in translation is a remarkable molecular machine called the ribosome. Ribosomes are made out of proteins and rRNAs (the "r" stands for "ribosomal").

I mentioned a few chapters ago that RNA can sometimes possess enzymatic activity. The translation process features two different kinds of functional RNAs: these rRNAs and tRNAs, which I'll introduce in a moment.

Returning to our processed mRNA, it is now in the cytoplasm. It carries the same coding information as the gene, with uracil (U) in place of thymine (T).

In addition to an mRNA, a ribosome, and all 20 amino acids, the other central players in translation are the tRNAs I just mentioned (the "t" stands for "transfer").

Humans have dozens of distinct tRNA types—roughly 40–50—each adapted to recognize specific codons and carry the corresponding amino acid to the ribosome.

Each tRNA has two functional ends: one carries a specific amino acid, and the other contains an anticodon that base-pairs with a codon on the mRNA.

Each tRNA has two functional ends: one carries a specific amino acid, and the other contains an anticodon that base-pairs with a codon on the mRNA—linking the language of nucleotides (As, Ts, Us, Cs, and Gs) to the language of proteins (amino acids).

A ribosome is able to decipher the mRNA and, in doing so, line up the correct amino acids in the right order.

One side point: even though there are 64 codons, the cell doesn’t need 64 tRNAs. This is possible because the third position in a codon is often more flexible, allowing one tRNA to recognize multiple codons.

Back to the mechanics of translation.

Ribosomes have three docking sites for tRNAs. Biologists call them the A (arrival), P (peptidyl), and E (exit) sites. I’ll refer to them as docking stations 1, 2, and 3, with docking station 1 at the front as the ribosome moves along the mRNA from left to right.

The ribosome first binds near the 5′ end of the mRNA (upstream of the gene) and then scans along it until it finds a start codon (usually AUG) within the translated region. Once found, that codon will be positioned at the base of docking station 2 (the middle one).

Given that the start codon is AUG, the first amino acid added must be methionine. Many tRNAs will sample the start codon, but only the correct one stays. Eventually, a tRNA with both the correct anticodon (UAC) and a methionine attached will lodge into docking station 2.

While this is occurring, the second mRNA codon will be positioned at the base of docking station 1. The ribosome then allows the next tRNA with the correct anticodon to arrive and lodge in that docking station.

Now we have two tRNAs--both with amino acids attached--in the ribosome docking stations 1 and 2 . When the tRNAs are in the docking stations, the two amino acids line up next to each. The ribosome forms a chemical bond between them and then transfers the growing chain to the tRNA in docking station 1.

Now the ribosome shifts forward by one codon, moving the empty, or "amino-acid-less," tRNA to docking station 3 (the exit site), the peptide-bearing tRNA to station 2 (the middle site), and opening docking station 1 (the front site) for the next incoming tRNA.

The ribosome again waits for the tRNA with the appropriate anticodon and amino acid to arrive at docking station 1. Once it does, this third amino acid will be chemically attached to the second. We now have a three-amino acid protein.

This continues until the ribosome reaches a stop codon. At that point, no matching tRNA binds; instead, a release factor (another protein) enters the ribosome, triggers release of the completed protein, and the ribosome dissociates from the mRNA.

With translation complete, the cell has turned a linear sequence of nucleotides into a functional protein. But this process depends on something we have largely taken for granted: that the DNA containing these genes is accessible in the first place.

In reality, DNA is tightly packed within the nucleus, and how it is organized plays an important role in determining which genes can be expressed.

In the next chapter, we’ll turn to how DNA is packaged—and how that packaging helps control the flow of genetic information.