Sequence, Structure and Context Preferences of Human RNA Binding Proteins

Domínguez, Daniel; Freese, Peter; Alexis, Maria S.; Su, Amanda; Hochman, Myles; Palden, Tsultrim; Bazile, Cassandra; Lambert, Nicole; Nostrand, Eric L. Van; Pratt, Gabriel A.; Yeo, G; Graveley, Brenton R.; Burge, Christopher B.

doi:10.1101/201996

Cited by 162 publications

(311 citation statements)

References 86 publications

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“…Many lncRNAs can regulate the expression of downstream target genes by forming complexes with RNA‐binding proteins, then acts as an oncogene or a suppressor oncogene . In this study, we found that knockdown of MAPKAPK5‐AS1 in CRC cells could lead to changes in related downstream genes, including p15 , p21 , p27 , p57 , KLF2 , and Trail .…”

Section: Discussionmentioning

confidence: 64%

“…In this study, we analyzed 2 sources Many lncRNAs can regulate the expression of downstream target genes by forming complexes with RNA-binding proteins, [27][28][29][30] then acts as an oncogene or a suppressor oncogene. [31][32][33][34][35] In this study, we found that knockdown of MAPKAPK5-AS1 in CRC cells could lead to changes in related downstream genes, including p15, p21, p27, p57, KLF2, and Trail. Among them, p21 has high basal expression abundance in CRC cells, which aroused our interest.…”

Section: Discussionmentioning

confidence: 66%

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Long noncoding RNA MAPKAPK5‐AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

Hui

Wang

et al. 2018

Cancer Science

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Colorectal cancer (CRC) is the third most common malignancy in the world, and long noncoding RNA (lncRNA) plays a critical role in carcinogenesis. Here, we report a novel lncRNA, MAPKAPK5‐AS1, that acts as a critical oncogene in CRC. In addition, we attempted to explore the functions of MAPKAPK5‐AS1 on tumor progression in vitro and in vivo. Quantitative RT‐PCR was used to examine the expression of MAPKAPK5‐AS1 in CRC tissues and cells. Expression of MAPKAPK5‐AS1 was significantly upregulated in 50 CRC tissues, and increased expression of MAPKAPK5‐AS1 was found to be associated with greater tumor size and advanced pathological stage in CRC patients. Knockdown of MAPKAPK5‐AS1 significantly inhibited proliferation and caused apoptosis in CRC cells. We also found that p21 is a target of MAPKAPK5‐AS1. In addition, we are the first to report that MAPKAPK5‐AS1 plays a carcinogenic role in CRC. MAPKAPK5‐AS1 is a novel prognostic biomarker and a potential therapeutic candidate for CRC cancer.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 66%

Long noncoding RNA MAPKAPK5‐AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

Hui

Wang

et al. 2018

Cancer Science

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“…Given our findings that FMRP localization targets were enriched for G-quadruplex sequences, we next sought to determine if FMRP directly interacted with G-quadruplex RNAs over other RNAs in vitro. To this end, we performed RNA Bind-n-Seq (RBNS), a quantitative and unbiased method that defines the specificity of a given RBP or RNA binding domain by incubating purified protein with a diverse pool of billions of random RNA sequences (Dominguez et al, 2018;Lambert et al, 2014;Taliaferro et al, 2016b). In this technique, the input RNA pool and proteinassociated RNA are sequenced using highthroughput sequencing.…”

Section: The Rgg Domain Of Fmrp Specifically Recognizes G-quadruplex mentioning

confidence: 99%

“…The RNA Bind-n-Seq assay was performed similar to previously described (Dominguez et al, 2018). Briefly, RNA with a random region of 40nt was prepared by in vitro transcription.…”

Section: Rna Bind-n-seq Protein Purification and Sequence Analysismentioning

confidence: 99%

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FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences

Goering

Hudish

Guzman

et al. 2019

Preprint

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The sorting of RNA molecules to distinct subcellular locations facilitates the activity of spatially restricted processes through local protein synthesis. This process affects thousands of transcripts yet precisely how these RNAs are trafficked to their destinations remains generally unclear. Here we have analyzed subcellular transcriptomes of FMRP-null mouse neuronal cells to identify transcripts that depend on FMRP for efficient transport to neurites. We found that these FMRP RNA localization targets contain a large enrichment of G-quadruplex sequences, particularly in their 3′ UTRs, suggesting that FMRP recognizes these sequences to promote the localization of transcripts that contain them. Fractionation of neurons derived from human Fragile X Syndrome patients revealed a high degree of conservation in the identity of FMRP localization targets between human and mouse as well as an enrichment of G-quadruplex sequences in human FMRP RNA localization targets. Using high-throughput RNA/protein interaction assays and single-molecule RNA FISH, we identified the RGG domain of FMRP as important for both interaction with G-quadruplex RNA sequences and the neuronal transport of G-quadruplex-containing transcripts. Finally, we used ribosome footprinting to identify translational regulatory targets of FMRP. The translational regulatory targets were not enriched for G-quadruplex sequences and were largely distinct from the RNA localization targets of FMRP, indicating that the two functions can be biochemically separated and are mediated through different target recognition mechanisms. These results establish a molecular mechanism underlying FMRP-mediated neuronal RNA localization and provide a framework for the elucidation of similar mechanisms governed by other RNA-binding proteins.

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Different recognition modes of G‐quadruplex RNA between two ALS/FTLD‐linked proteins TDP‐43 and FUS

2020

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Amyotrophic lateral sclerosis/frontotemporal lobar degeneration‐linked proteins, TDP‐43 and fused in sarcoma (FUS), bind to G‐quadruplex‐containing mRNAs and transport them to distal neurites for local translation. The specificity and mechanism of G4‐RNA binding, however, remain largely unsolved. Using purified full‐length TDP‐43 and FUS and a set of seven G4‐DNA/RNA, we compared their recognition properties of G4‐RNAs. Both TDP‐43 and FUS recognized and bound to G4‐DNA/RNAs, but the target selectivity differed between two proteins. TDP‐43 recognized only parallel‐stranded G4‐DNA/RNAs, leading to stabilize the G4 conformation. In contrast, FUS bound to all three types, parallel, hybrid, and antiparallel, of G4‐DNA/RNAs, resulting in deformation of the G4 structure. We then concluded that the target selectivity and the influence on G4 RNA structure differed between TDP‐43 and FUS.

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Sequence, Structure and Context Preferences of Human RNA Binding Proteins

Cited by 162 publications

References 86 publications

Long noncoding RNA MAPKAPK5‐AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

Long noncoding RNA MAPKAPK5‐AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences

Different recognition modes of G‐quadruplex RNA between two ALS/FTLD‐linked proteins TDP‐43 and FUS

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