Blood pressure homeostasis is maintained by a P311-TGF-β axis

P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311(–/–)) mice display learning and memory defects, but alterations in their vasculature have not been previously described. Here we report that P311(–/–) mice are markedly hypotensive with accompanying defects in vascular tone and VSMC contractility. Functional abnormalities in P311(–/–) mice resulted from decreased total and active levels of TGF-β1, TGF-β2, and TGF-β3 that arise as a specific consequence of decreased translation. Vascular hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-β1–TGF-β3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF-β1–TGF-β3 and subsequent hypertension. Consistent with findings attained in mouse models, arteries recovered from hypertensive human patients displayed increased P311 expression. Thus, we identified P311 as the first protein known to modulate TGF-β translation and the first pan-regulator of TGF-β expression under steady-state conditions. Together, our findings point to P311 as a critical blood pressure regulator and establish a potential link between P311 expression and the development of hypertensive disease

Roles of protein subunits in RNA–protein complexes: Lessons from ribonuclease P

Ribonucleoproteins (RNP) are involved in many essential processes in life. However, the roles of RNA and protein subunits in an RNP complex are often hard to dissect. In many RNP complexes, including the ribosome and the Group II introns, one main function of the protein subunits is to facilitate RNA folding. However, in other systems, the protein subunits may perform additional functions, and can affect the biological activities of the RNP complexes. In this review, we use ribonuclease P (RNase P) as an example to illustrate how the protein subunit of this RNP affects different aspects of catalysis. RNase P plays an essential role in the processing of the precursor to transfer RNA (pre-tRNA) and is found in all three domains of life. While every cell has an RNase P (ribonuclease P) enzyme, only the bacterial and some of the archaeal RNase P RNAs (RNA component of RNase P) are active in vitro in the absence of the RNase P protein. RNase P is a remarkable enzyme in the fact that it has a conserved catalytic core composed of RNA around which a diverse array of protein(s) interact to create the RNase P holoenzyme. This combination of highly conserved RNA and altered protein components is a puzzle that allows the dissection of the functional roles of protein subunits in these RNP complexes. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 79–89, 2004Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34329/1/10521_ftp.pd