Which transport mechanism does NOT require a signal sequence?
Small metabolites, ions, nucleotides and proteins smaller than roughly 40 kilodaltons equilibrate between nucleus and cytoplasm without peptide targeting signals because the nuclear pore complex forms a large aqueous channel about nine nanometers wide lined with intrinsically disordered FG-repeat nucleoporins that act as a size-selective hydrogel sieve allowing diffusion along concentration gradients. This passive process supports rapid exchange of ATP, GTP, amino acids and small second messengers needed for transcription, DNA replication and growth, without consuming energy. By contrast, larger macromolecules exceeding the diffusion limit rely on active receptor-mediated transport. Mitochondrial proteins use amphipathic N-terminal presequences recognized by TOM20 receptor, ER secretory proteins carry hydrophobic signal peptides bound by signal recognition particle, and ER-Golgi trafficking requires coat-dependent capture via di-acidic or KDEL retrieval motifs. NLS enriched in lysine and arginine and leucine-rich NES recognized by importin and exportin families provide specificity for nuclear crossing. Therefore nuclear flux of small species represents receptor-independent equilibration that conserves energy while permitting continuous communication between genome and cytosolic metabolism essential for cell cycle progression, signal transduction and maintenance of nucleotide pools across compartments.
Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 12: Nuclear Pore Complex and Passive Diffusion of Small Molecules.