The Rrp6 C-terminal domain binds RNA and activates the nuclear RNA exosome

Abstract

The eukaryotic RNA exosome is an essential, multi-subunit complex that catalyzes RNA turnover, maturation, and quality control processes. Its non-catalytic donut-shaped core includes 9 subunits that associate with the 3′ to 5′ exoribonucleases Rrp6, and Rrp44/Dis3, a subunit that also catalyzes endoribonuclease activity. Although recent structures and biochemical studies of RNA bound exosomes from S. cerevisiae revealed that the Exo9 central channel guides RNA to either Rrp6 or Rrp44 using partially overlapping and mutually exclusive paths, several issues related to RNA recruitment remain. Here, we identify activities for the highly basic Rrp6 C-terminal tail that we term the ‘lasso’ because it binds RNA and stimulates ribonuclease activities associated with Rrp44 and Rrp6 within the 11-subunit nuclear exosome. Stimulation is dependent on the Exo9 central channel, and the lasso contributes to degradation and processing activities of exosome substrates in vitro and in vivo. Finally, we present evidence that the Rrp6 lasso may be a conserved feature of the eukaryotic RNA exosome.

pH‐dependent conformational dynamics of beta‐secretase 1: A molecular dynamics study

“…This loop was constructed using homology modeling from the Structure Prediction Wizard module of Schrödinger's Prime program . First, the FASTA sequence of the protein including the missing loop region was obtained from UniProt . Then, utilizing the homologs found by the BLAST search algorithm, a chimera model containing the missing loop region was built.…”

“…[39][40][41] First, the FASTA sequence of the protein including the missing loop region was obtained from UniProt. 42 Then, utilizing the homologs found by the BLAST search algorithm, 43 a chimera model containing the missing loop region was built. Finally, the homology-modeled loop region was energy-refined for relaxation using the Refine Loops panel of the Prime program.…”

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

“…Interestingly, Dis3 activation requires two domains of Rrp6, its catalytic Exo/HRDC module and its C-terminal tail, termed the RNA lasso ( Fig. 1; Wasmuth and Lima 2017). While the catalytic domain binds the S1/KH ring to presumably widen the central channel, the C-terminal domain binds RNA to enhance Rrp6 and Dis3 activities on a variety of RNA substrates.…”

Molecular convergence and positive selection associated with the evolution of symbiont transmission mode in stony corals

“…To examine molecular convergence and positive selection, we compared homologous coding sequences from transcriptomic data of 25 coral species. First, protein coding sequences were predicted from the transcriptomic data based on open reading frames and sequence homology to known proteins (27) and protein domains (28), and FastOrtho (29) was used to assign sequences to preliminary orthologous groups (N = 106,300 groups). A subset of 1,196 single-copy orthologous groups with at least 20 of the 28 taxa represented was used to construct a species tree (Fig.…”