Why do proteins that move to the nucleus tend not to contain an N-terminal signal peptide?

Answer 1

The N-terminal signal peptide is recognised by SRP (signal recognition particle). SRP directs the peptide to translocons on the membrane of the rough endoplasmic reticulum, usually during translation (co-translational). The translocon is responsible for the transport of the protein into the endoplasmic reticulum, from which it will either be secreted or sent to organelles such as the mitochondria, chloroplasts, endosome, lysomome and peroxisome. These organelles require that proteins go through the endoplasmic reticulum as the proteins are incorporated into the organelles through vesicular transport, as they do not have their own uptake methods.

Proteins destined for the nucleus are not sent through the endoplasmic reticulum, as the method of transport into the nucleus is not vesicular. Instead, the nucleus has its own pores capable of translocating proteins into the nucleus.

Small objects can pass through these nuclear pores by passive transport, but anything bigger than 40kDa requires a special mechanism. Proteins destined for the nucelus have a nuclear-localisation signal (NLS) instead of the N-terminal signal peptide. The NLS is a seven residue sequence of basic amino acids at the C-terminus.