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Review
. 2021 Nov 6;46(2):73-78.
doi: 10.1247/csf.21041. Epub 2021 Sep 3.

Nuclear RNA Regulation by XRN2 and XTBD Family Proteins

Ilkin Aygün  1 , Takashi S Miki  1
Affiliations
Review

Nuclear RNA Regulation by XRN2 and XTBD Family Proteins

Ilkin Aygün et al. Cell Struct Funct. .

Abstract

XRN2 is a 5'-to-3' exoribonuclease that is predominantly localized in the nucleus. By degrading or trimming various classes of RNA, XRN2 contributes to essential processes in gene expression such as transcription termination and ribosome biogenesis. Despite limited substrate specificity in vitro, XRN2 targets a specific subset of RNA by interacting with other proteins in cells. Here we review the functions of proteins that have an evolutionarily conserved XRN2-binding domain, XTBD. These proteins modulate activity of XRN2 by stabilizing it, controlling its subcellular localization or recruiting it to specific RNA targets, and thereby impact on various cellular processes.Key words: RNA regulation, XRN2, XTBD, ribosome biogenesis, subcellular localization.

Keywords: RNA regulation; XRN2; XTBD; ribosome biogenesis; subcellular localization.

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Figures

Fig. 1
Fig. 1
XTBD family proteins. (A) XTBDs of Homo sapiens (Hs) NKRF (39–111 aa), CDKN2AIP (19–124 aa), and CDKN2AIPNL (25–113 aa), Danio rerio (Dr) CDKN2AIP (24–114 aa, 184–276 aa), Drosophila melanogaster (Dm) CG31301 (34–118 aa), Caenorhabditis elegans (Ce) PAXT-1 (7–87 aa), and Tetrahymena thermophila (Tt) Tan1 (49–106 aa) are aligned by Clustal Omega (https://www.ebi.ac.uk/Tools/msa/clustalo/) and visualized by Jalview (https://www.jalview.org/), based on the Pfam database. The most frequent amino acids are in blue and similar amino acids in light blue, based on BLOSUM62. A highly conserved tyrosine required for interaction with XRN2 is marked with an asterisk. (B) Domain architectures of XTBD family proteins based on the Pfam database. Amino acid numbers relative to the first methionine are shown. XTBD: XRN-Two Binding Domain; dsrm: Double-stranded RNA binding motif; G-patch: G-patch domain; R3H: R3H domain. Amino acid numbers relative to the first methionine are shown.
Fig. 2
Fig. 2
Model for XRN2 regulation by NKRF and CDKN2AIP in ribosome biogenesis. NKRF promotes localization of XRN2 to pre-rRNA for processing. It is unclear where NKRF initially recognizes XRN2, in the nucleoplasm or the nucleolus. CDKN2AIP sequesters XRN2 in the nucleoplasm, thereby suppressing pre-rRNA processing. SAMMSON promotes nucleolar localization of XRN2 by sequestering CDKN2AIP in the cytoplasm and/or by interfering with CDKN2AIP-XRN2 interaction in the nucleoplasm in melanoma cells. Competition between NKRF and CDKN2AIP for XRN2 binding and whether SAMMSON promotes NKRF-XRN2 interaction remain to be investigated.
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