Model for mRNA buffering mediated by the nucleo-cytoplasmic shuttling of RNA-binding factors. Cartoon model showing the crosstalk pathways from the nucleus to the cytoplasm (direct), and from the cytoplasm to the nucleus (reverse). Buffering factors (BF) (colored ovals) shuttle between the cytoplasm and the nucleus. They are imported to the nucleus when they become free of mRNAs, either when mRNAs are degraded (bottom) by decay machineries (green and orange pacman) or before an equilibrium is struck between the bound and free states (top). BF can travel back to the cytoplasm by cotranscriptional imprinting in either mRNA sequences (black ovals) or poly(A) tails (red ovals). BFs can accompany mRNAs to p-bodies or other kinds of liquid droplets where they become separated from the soluble and translatable pool by a phase transition. Synthesis (SR) and degradation (DR) rates are adjusted for [mRNA]t buffering due to the stimulating activity of the nuclear BF in RNA pol II transcription and the (direct or indirect) relation of BF to mRNA degradation in the cytoplasm. mRNAs may have a cap (c) or phosphate (P) on their 5′-end, and may be translated by the ribosomes in the cytoplasm. Figure created with the help of BioRender.
