Cellular intelligence: pure automaticity (Evolution)

by David Turell @, Saturday, December 11, 2021, 00:48 (41 days ago) @ David Turell

Tight controls of nuclear transcriptions:


The TFIID component, TAF7, has been extensively characterized as essential for transcription and is critical for cell proliferation and differentiation. Here, we report that TAF7 is a previously unknown RNA chaperone that contributes to the regulation of protein synthesis. Mechanistically, TAF7 binds RNAs in the nucleus and delivers them to cytoplasmic polysomes. A broad spectrum of target RNA species, including the HIV-1 transactivation response element, binds TAF7 through consensus CUG motifs within the 3′ untranslated region. Export to the cytoplasm depends on a TAF7 nuclear export signal and occurs by an exportin 1–dependent pathway. Notably, disrupting either TAF7’s RNA binding or its export from the nucleus results in retention of target messenger RNAs in the nucleus and reduced levels of the protein products of TAF7-target RNAs. Thus, TAF7, an essential transcription factor, plays a key role in the regulation of RNA translation, thereby potentially connecting these processes."


"Translation depends on RNA export by TAF7
In the cytoplasm, TAF7 contributes to translation. Thus, TAF7 is associated with a large 440-kDa complex that consists of ribosomal proteins; no other TFIID components are found within the complex. TAF7 is associated with polysomes through its interaction with RNA. Furthermore, retention of TAF7 in the nucleus, by mutation of its NES, results in a global decrease in translation and a decrease in the levels of proteins whose RNAs are bound by TAF7. Mutation of the TAF7 RBD similarly results in decreased global translation. Thus, a novel function of TAF7 is to deliver its RNA cargo to polysomes for translation. Consistent with TAF7 regulating transcription of and binding to a broad spectrum of RNA species, this seems to be a general function not restricted to a specific functional subset of transcripts."

"TAF7 coordinates transcription and translation
The present studies provide evidence for the coordination of transcription and translation by the TFIID component, TAF7. We have shown that TAF7, which regulates each step in transcription initiation, also regulates translation. The mechanism by which TAF7 regulates translation is through its binding to and chaperoning of a broad spectrum of RNA species from the nucleus to the cytoplasm, delivering them to polysomes to promote global protein synthesis. On the basis of our findings, we propose a model in which TAF7 integrates transcription and translation machineries that operate in distinct cellular compartments (Fig. 7). In the nucleus, TAF7 regulates transcription through its regulation of the enzymatic activities of TAF1/TFIID, TFIIH, BRD4, and P-TEFb, traveling with the elongation complex. It then functions as an RNA chaperone, binding RNA and transporting it to the cytoplasm. In the cytoplasm, TAF7 delivers its RNA cargo to polysomes, thereby contributing to translation. Of note, the TAF7 NLS overlaps with its RBD: Deletion of the NLS abrogates RNA binding. In the cytoplasm, RNA bound to TAF7 would mask the NLS, preventing cytoplasmic TAF7-RNA complexes from being imported back into the nucleus. After delivering RNA to polysomes, TAF7 is released from the RNA, thereby exposing the NLS and enabling shuttling of TAF7 back to the nucleus. In conclusion, TAF7 is a multifunctional regulator of gene expression, which coordinates many of the complex steps of gene expression."

Comment: Controlling protein must be precise to produce the right products. There is no other interpretation but that these processes are totally automatic under very tight controls, by design. No cellular decisions required.

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