Biogenesis of RNase P RNA from an intron requires co-assembly with cognate protein subunits

Palsule, Geeta; Gopalan, Venkat; Simcox, Amanda

doi:10.1093/nar/gkz572

Cited by 3 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, knocking down Pop5, Rpp14, Rpp21 or Rpp30 does not significantly affect the expression levels of RPR. The role of the Rpp20–Rpp25–Pop1–Pop4 subcomplex in the production of RPR is essential and highlights the importance of protein subunit interactions for the assembly of the RNase P holoenzyme, which is coupled to RPR transcription [ 93 ].…”

Section: Sub-complexes Of Rnase P Protein Subunitsmentioning

confidence: 99%

The Dynamic Network of RNP RNase P Subunits

Shaukat

Kaliatsi

Skeparnias

et al. 2021

IJMS

View full text Add to dashboard Cite

Ribonuclease P (RNase P) is an important ribonucleoprotein (RNP), responsible for the maturation of the 5′ end of precursor tRNAs (pre-tRNAs). In all organisms, the cleavage activity of a single phosphodiester bond adjacent to the first nucleotide of the acceptor stem is indispensable for cell viability and lies within an essential catalytic RNA subunit. Although RNase P is a ribozyme, its kinetic efficiency in vivo, as well as its structural variability and complexity throughout evolution, requires the presence of one protein subunit in bacteria to several protein partners in archaea and eukaryotes. Moreover, the existence of protein-only RNase P (PRORP) enzymes in several organisms and organelles suggests a more complex evolutionary timeline than previously thought. Recent detailed structures of bacterial, archaeal, human and mitochondrial RNase P complexes suggest that, although apparently dissimilar enzymes, they all recognize pre-tRNAs through conserved interactions. Interestingly, individual protein subunits of the human nuclear and mitochondrial holoenzymes have additional functions and contribute to a dynamic network of elaborate interactions and cellular processes. Herein, we summarize the role of each RNase P subunit with a focus on the human nuclear RNP and its putative role in flawless gene expression in light of recent structural studies.

show abstract

Section: Sub-complexes Of Rnase P Protein Subunitsmentioning

confidence: 99%

The Dynamic Network of RNP RNase P Subunits

Shaukat

Kaliatsi

Skeparnias

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160

Moir

Lavados

Lee

et al. 2021

Gene

View full text Add to dashboard Cite

Mutations in RNA polymerase III (Pol III) cause hypomeylinating leukodystrophy (HLD) and neurodegeneration in humans. POLR3A and POLR3B, the two largest Pol III subunits, together form the catalytic center and carry the majority of disease alleles. Disease-causing mutations include invariant and highly conserved residues that are predicted to negatively affect Pol III activity and decrease transcriptional output. A subset of HLD missense mutations in POLR3A cluster in the pore region that provides nucleotide access to the Pol III active site. These mutations were engineered at the corresponding positions in the Saccharomyces cerevisiae homolog, Rpc160, to evaluate their functional deficits. None of the mutations caused a growth or transcription phenotype in yeast. Each mutation was combined with a frequently occurring pore mutation, POLR3A G672E, which was also wild-type for growth and transcription. The double mutants showed a spectrum of phenotypes from wild-type to lethal, with only the least fit combinations showing an effect on Pol III transcription. In one slow-growing temperaturesensitive mutant the steady-state level of tRNAs was unaffected, however global tRNA synthesis was compromised, as was the synthesis of RPR1 and SNR52 RNAs. Affinity-purified mutant Pol III was broadly defective in both factor-independent and factor-dependent transcription in vitro across genes that represent the yeast Pol III transcriptome. Thus, the robustness of yeast to Pol III leukodystrophy mutations in RPC160 can be overcome by a combinatorial strategy..

show abstract

Functional characterization ofPolr3ahypomyelinating leukodystrophy mutations in theS. cerevisiaehomolog,RPC160

Moir

Lavados

Lee

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractMutations in RNA polymerase III (Pol III) cause hypomeylinating leukodystrophy (HLD) and neurodegeneration in humans. POLR3A and POLR3B, the two largest Pol III subunits, together form the catalytic center and carry the majority of disease alleles. Disease-causing mutations include invariant and highly conserved residues that are predicted to negatively affect Pol III activity and decrease transcriptional output. A subset of HLD missense mutations in POLR3A cluster in the pore region that provides nucleotide access to the Pol III active site. These mutations were engineered at the corresponding positions in the Saccharomyces cerevisiae homolog, Rpc160, to evaluate their functional deficits. None of the mutations caused a growth or transcription phenotype in yeast. Each mutation was combined with a frequently occurring pore mutation, POLR3A G672E, which was also wild-type for growth and transcription. The double mutants showed a spectrum of phenotypes from wild-type to lethal, with only the least fit combinations showing an effect on Pol III transcription. In one slow-growing temperature-sensitive mutant the steady-state level of tRNAs was unaffected, however global tRNA synthesis was compromised, as was the synthesis of RPR1 and SNR52 RNAs. Affinity-purified mutant Pol III was broadly defective in both factor-independent and factor-dependent transcription in vitro across genes that represent the yeast Pol III transcriptome. Thus, the robustness of yeast to Pol III leukodystrophy mutations in RPC160 can be overcome by a combinatorial strategy.

show abstract

Biogenesis of RNase P RNA from an intron requires co-assembly with cognate protein subunits

Cited by 3 publications

References 44 publications

The Dynamic Network of RNP RNase P Subunits

The Dynamic Network of RNP RNase P Subunits

Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160

Functional characterization ofPolr3ahypomyelinating leukodystrophy mutations in theS. cerevisiaehomolog,RPC160

Contact Info

Product

Resources

About