CNOT1 contributes to small nuclear non-coding RNA maturation

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Abstract

CCR4-NOT complex plays a variety of functional roles in mRNA metabolism, including transcription, translation, and mRNA degradation. As of yet, it is unknown if CCR4-NOT has additional functions beyond those we know. It is possible to predict or uncover unknown functions of genes by using co-expressed network analysis. The analysis is based on the premise that functionally similar genes may exhibit similar expression patterns. Here we show that all CCR4-NOT complex subunit genes highly co-express with modulators of small nuclear noncoding RNA biogenesis, predicting that CCR4-NOT regulates the maturation of small nuclear noncoding RNA. In agreement with the prediction, knockdown of CNOT1 decreased the expression levels of small nuclear non-coding RNAs, such as scaRNAs and snoRNAs. The reduced expression of small nuclear non-coding RNA was independent of the canonical function of CCR4-NOT complex. However, the reduced expression was rescued by the co-suppression of RBM7, an RNA-binding protein that mediates exosomal degradation of misprocessed small nuclear non-coding RNA. These results suggest that CNOT1 contributes to small nuclear non-coding RNA maturation.

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