Translation of poly(A)-binding protein mRNA is regulated by growth conditions

Abstract

Translational efficiency of a minor group of mRNAs is regulated by serum levels in 3T6 fibroblasts. Included within this group is the poly(A)-binding protein (PABP) mRNA. We analyzed the distribution of PABP mRNA in polysome profiles and found a large percentage of this mRNA to be translationally repressed in both actively growing (approximately 60%) and resting cells (approximately 70%). Elevated serum levels induced a distinct bimodal distribution of this mRNA between actively translated and repressed fractions. Similarly, treatment of cells with low doses of cycloheximide also generated a partial shift of repressed PABP mRNA into the actively translated fraction. In an attempt to characterize the factors which regulate PABP mRNA translation we have identified the proteins which bind to this mRNA in vitro. Sequences within the 5' untranslated region were found to be sufficient for binding of all proteins to this mRNA. We suggest that this region and the proteins associated with it may be essential for translation control of PABP mRNA.

Feedback Inhibition of Poly(A)-binding Protein mRNA Translation

“…In fact, the Pabp1 gene behaves like a primary response gene. Stimulation of proliferation of mammalian cells in culture or in vivo results in increased Pabp1 synthesis (32)(33)(34)(35)(36)(37)). Control of the cellular level of Pabp1 usually occurs by regulating the translation of its mRNA.…”

“…Control of the cellular level of Pabp1 usually occurs by regulating the translation of its mRNA. Stimulation of proliferation of quiescent 3T3 cells by serum (34,35,37) or the same in liver cells by partial hepatectomy (37) results in the activation of translation of stored non-translated mRNAs. It is thought that an increase in the cellular Pabp1 level could alter translation and stability of some mRNAs.…”

Negative Control of the Poly(A)-binding Protein mRNA Translation Is Mediated by the Adenine-rich Region of Its 5′-Untranslated Region

“…Several studies indicated that PABP expression is regulated at the post-transcriptional level during the cell cycle (15)(16)(17)(18)(19)(20). In resting cells, the majority of cellular PABP mRNA was found in the non-translated state.…”

“…In resting cells, the majority of cellular PABP mRNA was found in the non-translated state. Following stimulation of growth by serum, a rapid transition of the mRNA to the translated state occurred in mouse fibroblasts (19,20). In contrast, during differentiation of murine myoblasts growth arrest resulted in the migration of repressed PABP mRNA to the translated state.…”

Cytoplasmic Protein mRNA Interaction Mediates cGMP-modulated Translational Control of the Asialoglycoprotein Receptor

“…Current evidence suggests that mRNAs in these functionally distinct fractions differ structurally or through the proteins they interact with (18). Within this group of mRNAs, most interactions between RNA and cytosolic proteins were defined by motifs localized to the 5Ј-UTR (19).…”