Box C/D snoRNP Autoregulation by a cis-Acting snoRNA in the NOP56 Pre-mRNA

TY - JOUR

T1 - Box C/D snoRNP Autoregulation by a cis-Acting snoRNA in the NOP56 Pre-mRNA

AU - Lykke-Andersen, Søren

AU - Ardal, Britt Kidmose

AU - Hollensen, Anne Kruse

AU - Damgaard, Christian Kroun

AU - Jensen, Torben Heick

PY - 2018/10/4

Y1 - 2018/10/4

N2 - Box C/D snoRNAs constitute a class of abundant noncoding RNAs that associate with common core proteins to form catalytic snoRNPs. Most of these operate in trans to assist the maturation of rRNAs by guiding and catalyzing the 2′-O-methylation of specific nucleotides. Here, we report that the human intron-hosted box C/D snoRNA snoRD86 acts in cis as a sensor and master switch controlling levels of the limiting snoRNP core protein NOP56, which is important for proper ribosome biogenesis. Our results support a model in which snoRD86 adopts different RNP conformations that dictate the usage of nearby alternative splice donors in the NOP56 pre-mRNA. Excess snoRNP core proteins prevent further production of NOP56 and instead trigger the generation of a cytoplasmic snoRD86-containing NOP56-derived lncRNA via the nonsense-mediated decay pathway. Our findings reveal a feedback mechanism based on RNA structure that controls the precise coordination between box C/D snoRNP core proteins and global snoRNA levels. Lykke-Andersen et al. demonstrate that a specific human intron-hosted box C/D snoRNA controls the alternative splicing of its host transcript via a structural “switching” mechanism that serves to coordinate global levels of snoRNAs and protein partners. This function is entirely different from the canonical function of snoRNAs in ribosome biogenesis.

AB - Box C/D snoRNAs constitute a class of abundant noncoding RNAs that associate with common core proteins to form catalytic snoRNPs. Most of these operate in trans to assist the maturation of rRNAs by guiding and catalyzing the 2′-O-methylation of specific nucleotides. Here, we report that the human intron-hosted box C/D snoRNA snoRD86 acts in cis as a sensor and master switch controlling levels of the limiting snoRNP core protein NOP56, which is important for proper ribosome biogenesis. Our results support a model in which snoRD86 adopts different RNP conformations that dictate the usage of nearby alternative splice donors in the NOP56 pre-mRNA. Excess snoRNP core proteins prevent further production of NOP56 and instead trigger the generation of a cytoplasmic snoRD86-containing NOP56-derived lncRNA via the nonsense-mediated decay pathway. Our findings reveal a feedback mechanism based on RNA structure that controls the precise coordination between box C/D snoRNP core proteins and global snoRNA levels. Lykke-Andersen et al. demonstrate that a specific human intron-hosted box C/D snoRNA controls the alternative splicing of its host transcript via a structural “switching” mechanism that serves to coordinate global levels of snoRNAs and protein partners. This function is entirely different from the canonical function of snoRNAs in ribosome biogenesis.

KW - alternative splicing

KW - autoregulation

KW - box C/D snoRNA

KW - box C/D snoRNP assembly

KW - non-coding RNA

KW - NOP56

KW - ribosome biogenesis

KW - snoRD86

KW - SPA-lncRNA

UR - http://www.scopus.com/inward/record.url?scp=85054447103&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2018.08.017

DO - 10.1016/j.molcel.2018.08.017

M3 - Journal article

C2 - 30220559

AN - SCOPUS:85054447103

SN - 1097-2765

VL - 72

SP - 99-111.e1-e5

JO - Molecular Cell

JF - Molecular Cell

IS - 1

ER -