Rege-1 promotes C. elegans survival by modulating IIS and TOR pathways.

Metabolic pathways are known to sense the environmental stimuli and result in physiological adjustments. The responding processes need to be tightly controlled. Here, we show that upon encountering P.

Biogenesis of spermatogenesis small RNAs is initiated by a zc3h12a-like ribonuclease.

Small RNAs regulate spermatogenesis across species ranging from to humans. In , two Argonaute proteins, ALG-3 and ALG-4, and their associated 26G-small RNAs are essential for spermiogenesis at 25°C. The 26G-small RNAs are antisense to their target mRNAs and produced by the RNA-dependent RNA polymerase, RRF-3.

Poly(U)-specific endoribonuclease ENDOU promotes translation of human CHOP mRNA by releasing uORF element-mediated inhibition.

Upstream open reading frames (uORFs) are known to negatively affect translation of the downstream ORF. The regulatory proteins involved in relieving this inhibition are however poorly characterized. In response to cellular stress, eIF2α phosphorylation leads to an inhibition of global protein synthesis, while translation of specific factors such as CHOP is induced.

Structural Mechanism for the Fidelity Modulation of DNA Polymerase λ.

The mechanism of DNA polymerase (pol) fidelity is of fundamental importance in chemistry and biology. While high-fidelity pols have been well studied, much less is known about how some pols achieve medium or low fidelity with functional importance. Here we examine how human DNA polymerase λ (Pol λ) achieves medium fidelity by determining 12 crystal structures and performing pre-steady-state kinetic analyses.

The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression.

Ribosome biogenesis governs protein synthesis. NIFK is transactivated by c-Myc, the key regulator of ribosome biogenesis. The biological function of human NIFK is not well established, except that it has been shown to interact with Ki67 and NPM1.

A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi.

Effective silencing by RNA-interference (RNAi) depends on mechanisms that amplify and propagate the silencing signal. In some organisms, small-interfering RNAs (siRNAs) are amplified from target mRNAs by RNA-dependent RNA polymerase (RdRP). Both RdRP recruitment and mRNA silencing require Argonaute proteins, which are generally thought to degrade RNAi targets by directly cleaving them.

Dissecting functional cooperation among protein subunits in archaeal RNase P, a catalytic ribonucleoprotein complex.

RNase P catalyzes the Mg(2)(+)-dependent 5'-maturation of precursor tRNAs. Biochemical studies on the bacterial holoenzyme, composed of one catalytic RNase P RNA (RPR) and one RNase P protein (RPP), have helped understand the pleiotropic roles (including substrate/Mg(2+) binding) by which a protein could facilitate RNA catalysis. As a model for uncovering the functional coordination among multiple proteins that aid an RNA catalyst, we use archaeal RNase P, which comprises one catalytic RPR and at least four RPPs.

Functional reconstitution and characterization of Pyrococcus furiosus RNase P.

RNase P, which catalyzes the magnesium-dependent 5'-end maturation of tRNAs in all three domains of life, is composed of one essential RNA and a varying number of protein subunits depending on the source: at least one in bacteria, four in archaea, and nine in eukarya. To address why multiple protein subunits are needed for archaeal/eukaryal RNase P catalysis, in contrast to their bacterial relative, in vitro reconstitution of these holoenzymes is a prerequisite. Using recombinant subunits, we have reconstituted in vitro the RNase P holoenzyme from the thermophilic archaeon Pyrococcus furiosus (Pfu) and furthered our understanding regarding its functional organization and assembly pathway(s).

Structure of Mth11/Mth Rpp29, an essential protein subunit of archaeal and eukaryotic RNase P.

We have determined the solution structure of Mth11 (Mth Rpp29), an essential subunit of the RNase P enzyme from the archaebacterium Methanothermobacter thermoautotrophicus (Mth). RNase P is a ubiquitous ribonucleoprotein enzyme primarily responsible for cleaving the 5' leader sequence during maturation of tRNAs in all three domains of life. In eubacteria, this enzyme is made up of two subunits: a large RNA ( approximately 120 kDa) responsible for mediating catalysis, and a small protein cofactor ( approximately 15 kDa) that modulates substrate recognition and is required for efficient in vivo catalysis.

Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme.

Bacterial ribonuclease P (RNase P), an enzyme involved in tRNA maturation, consists of a catalytic RNA subunit and a protein cofactor. Comparative phylogenetic analysis and molecular modeling have been employed to derive secondary and tertiary structure models of the RNA subunits from Escherichia coli (type A) and Bacillus subtilis (type B) RNase P. The tertiary structure of the protein subunit of B.