Integrative omics indicate FMRP sequesters mRNA from translation and deadenylation in human neuronal cells

Kurosaki, Tatsuaki; Mitsutomi, Shuhei; Hewko, Alexander; Akimitsu, Nobuyoshi; Maquat, Lynne E.

doi:10.1016/j.molcel.2022.10.018

Cited by 10 publications

(14 citation statements)

References 103 publications

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“…We next performed RNA pulldown coupled with stable isotope labeling by amino acids in cell culture (SILAC) mass spectrometric analysis (RNA pulldown‐SILAC‐MS) to identify the post‐transcriptional regulators of SMIM26. SILAC has been widely used in the identification of RNA‐binding proteins (RBPs) that are involved in protein translation (Boulon et al , 2010; Casas‐Vila et al , 2020; Kurosaki et al , 2022). Biotinylated LINC00493 RNA was employed for pulldown in the equal lysates of SILAC labeling HEK293T (heavy) and ACHN (light), followed by mass spectrometric identification (Appendix Fig S5).…”

Section: Resultsmentioning

confidence: 99%

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

Meng

et al. 2023

EMBO Reports

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Human microproteins encoded by long non‐coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493‐encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA‐binding protein PABPC4 and transferred to ribosomes for translation of a 95‐amino‐acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N‐terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK‐mediated AKT phosphorylation. Moreover, the formation of the SMIM26‐AGK‐SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493‐encoded microprotein SMIM26 and establishes its anti‐metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers.

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Section: Resultsmentioning

confidence: 99%

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

Meng

et al. 2023

EMBO Reports

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“…Given the critical role of FMRP in brain function, numerous studies have focused on the transcripts it binds and regulates [ 18 , 19 ]. Cross-linking immunoprecipitation (CLIP) is a highly efficient, commonly used method to analyze protein interactions with RNA [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

FMRP binds Per1 mRNA and downregulates its protein expression in mice

Tang

Zhang

et al. 2023

Mol Brain

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FMRP, an RNA-binding protein, has previously shown to be involved in regulation of circadian rhythms in flies and mice. However, the molecular mechanism remains elusive. Here we demonstrate that core circadian component Per1 mRNA was a target of FMRP and the association leads to reduced PER1 expression. In Fmr1 KO mice, the oscillation of PER1 protein expression was significantly affected in a temporal and tissue-dependent pattern when compared to WT mice. Our work thus identified Per1 mRNA as a novel target of FMRP and suggested a potential role of FMRP in regulation of circadian function.

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“…Notably, NMD, like FMRP expression, typifies all mammalian cells [ 1 , 2 ]. It was recently found that FMRP is, as a rule, enriched on most if not all NMD targets via binding to the essential NMD factor UPF1 [ 3 ], if not also by direct FMRP binding to GC-rich and structured sequences [ 4 ]. Additionally, in SH-SY5Y cells, minimally one-third of FMRP-bound mRNAs are NMD targets [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells

Kurosaki,

Rambout,

Maquat

2024

Genome Biol

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In non-polarized cells, nonsense-mediated mRNA decay (NMD) generally begins during the translation of newly synthesized mRNAs after the mRNAs are exported to the cytoplasm. Binding of the FMRP translational repressor to UPF1 on NMD targets mainly inhibits NMD. However, in polarized cells like neurons, FMRP additionally localizes mRNAs to cellular projections. Here, we review the literature and evaluate available transcriptomic data to conclude that, in neurons, the translation of physiologic NMD targets bound by FMRP is partially inhibited until the mRNAs localize to projections. There, FMRP displacement in response to signaling induces a burst in protein synthesis followed by rapid mRNA decay.

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Integrative omics indicate FMRP sequesters mRNA from translation and deadenylation in human neuronal cells

Cited by 10 publications

References 103 publications

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

LINC00493‐encoded microprotein SMIM26 exerts anti‐metastatic activity in renal cell carcinoma

FMRP binds Per1 mRNA and downregulates its protein expression in mice

FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells

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