An RNA-Binding Chameleon

Abstract

The arginine-rich RNA binding motif is found in a wide variety of proteins, including several viral regulatory proteins. Although related at the primary sequence level, arginine-rich domains from different proteins adopt different conformations depending on the RNA site recognized, and in some cases fold only in the context of RNA. Here we show that the RNA binding domain of the Jembrana disease virus (JDV) Tat protein is able to recognize two different TAR RNA sites, from human and bovine immunodeficiency viruses (HIV and BIV, respectively), adopting different conformations in the two RNA contexts and using different amino acids for recognition. In addition to the conformational differences, the JDV domain requires the cyclin T1 protein for high-affinity binding to HIV TAR, but not to BIV TAR. The "chameleon-like" behavior of the JDV Tat RNA binding domain reinforces the concept that RNA molecules can provide structural scaffolds for protein folding, and suggests mechanisms for evolving distinct RNA binding specificities from a single multifunctional domain.

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

“…Compared with the sequences of wild-type B-and E-Tat at the downstream of this basic domain, the C-Tat has further several variations such as Glu 63 . The Ser 57 and Glu 63 were highly conserved among subtype C isolates reported previously (Fig. 5) ) as well as the above mentioned mutant Tats of subtypes B and C. The luciferase activities of B-M2 and C-M2 were greatly affected.…”

“…The higher Tat activity, despite of LTRs from all three subtypes, was obtained by subtype C compared with those by subtypes B and E. This higher C-Tat activity was derived from the variation at two amino acid residues (Ser 57 and Glu 63 in place of Arg 57 and Gln 63 of subtypes B and E).…”

“…4D). Thus, Ser 57 at the basic domain of C-Tat could have had some contribution to the higher transcriptional activity.…”

HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b

“…The former is observed, for example, in tRNA and polypeptide release factor binding to the same domain of ribosome (36) and in TAFII230 and TATA box element DNA binding to TATA-binding protein (37). The latter is observed in interactions between RNA and arginine-rich motifs (38). The N-terminal part of the HEXIM1 NLS is almost perfectly aligned with the TAR RNA-binding motif of the HIV-1 Tat protein (10).…”

“…The N-terminal part of the HEXIM1 NLS is almost perfectly aligned with the TAR RNA-binding motif of the HIV-1 Tat protein (10). It is known that argininerich motifs from different proteins adopt different conformations dependent on the RNA sites recognized and in some cases fold only in the presence of RNA (38). The formation of the Tat͞TAR͞P-TEFb complex in HIV-infected cells may, therefore, compete and preclude the formation of the inactive 5.…”