ALYREF mainly binds to the 5′ and the 3′ regions of the mRNA in vivo

Shi, Min; Zhang, Heng; Wu, Xudong; He, Zhisong; Wang, Lantian; Yin, Shanye; Tian, Bin; Li, Guohui; Cheng, Hong

doi:10.1093/nar/gkx597

Cited by 95 publications

(99 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2B). Similarly, the association of ZC3H11A at the 3' end is consistent with iCLIP signal observed for TREX complex component ALYREF [56] and provides further transcriptome-wide evidence to support the observation that ZC3H11A plays an essential role in export of polyadenylated mRNA through interaction with the TREX complex [57]. As we continue to profile additional RBPs, these results suggest it should become possible to predict RBP function with increasing resolution based on association patterns.…”

Section: Inference Of Rbp Function Based On Eclip Enrichment Patternssupporting

confidence: 81%

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

Nostrand

Pratt

Yee

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractA critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enabled mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale integrated analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the large-scale mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Here we describe our analysis of 223 enhanced (eCLIP) datasets characterizing 150 RBPs in K562 and HepG2 cell lines, revealing a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multi-copy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation (enabling identification of branch points with single-nucleotide resolution) and provides genome-wide validation for a branch point-based scanning model for 3’ splice site recognition. Further, we show that eCLIP peak co-occurrences across RBPs enables the discovery of novel co-interacting RBPs. Finally, we present a protocol for visualization of RBP:RNA complexes in the eCLIP workflow using biotin and standard chemiluminescent visualization reagents, enabling simplified confirmation of ribonucleoprotein enrichment without radioactivity. This work illustrates the value of integrated analysis across eCLIP profiling of RBPs with widely distinct functions to reveal novel RNA biology. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.

show abstract

Section: Inference Of Rbp Function Based On Eclip Enrichment Patternssupporting

confidence: 81%

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

Nostrand

Pratt

Yee

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition to SLBP and Lsm11, ALYREF was found to directly interact with ARS2 and CstF64 (Fan et al, 2017;Shi et al, 2017), which have been implicated in histone mRNA processing as well (Gruber et al, 2012;Romeo et al, 2014). We also provide evidence that U7-snRNP is important for 3 0 -end processingdependent ALYREF recruitment.…”

supporting

confidence: 51%

“…We also provide evidence that U7-snRNP is important for 3 0 -end processingdependent ALYREF recruitment. In addition to SLBP and Lsm11, ALYREF was found to directly interact with ARS2 and CstF64 (Fan et al, 2017;Shi et al, 2017), which have been implicated in histone mRNA processing as well (Gruber et al, 2012;Romeo et al, 2014). It is possible that these processing factors also contribute to 3 0 -end processing-dependent ALYREF recruitment.…”

mentioning

confidence: 97%

ALYREF links 3′‐end processing to nuclear export of non‐polyadenylated mRNA s

Fan

Wang

et al. 2019

The EMBO Journal

Self Cite

View full text Add to dashboard Cite

The RNA‐binding protein ALYREF plays key roles in nuclear export and also 3′‐end processing of polyadenylated mRNAs, but whether such regulation also extends to non‐polyadenylated RNAs is unknown. Replication‐dependent (RD)‐histone mRNAs are not polyadenylated, but instead end in a stem‐loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD‐histone mRNAs. SL‐binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre‐mRNA 3′‐end processing by facilitating U7‐snRNP recruitment through physical interaction with the U7‐snRNP‐specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3′‐end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3′‐end processing and nuclear export of non‐polyadenylated mRNAs.

show abstract

“…The evolutionarily conserved TRanscription‐EXport (TREX) complex consisting of the THO subcomplex with ALYREF and Uap56 couples pre‐mRNA transcription, 3′‐end formation and subsequent nuclear export (Chanarat, Burkert‐Kautzsch, Meinel, & Sträßer, ; Katahira, ; Katahira et al, ; Katahira & Yoneda, ; Shi et al, ). Previously, we showed that knockdown of THOC5, an RNA binding component of human THO (hTHO), in HeLa cells perturbs nuclear export of HSP70 mRNA, resulting in accumulation of the mRNA at transcriptional foci (Katahira, Inoue, Hurt, & Yoneda, ).…”

Section: Introductionmentioning

confidence: 99%

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

et al. 2019

View full text Add to dashboard Cite

A multiprotein complex, THO/TREX, couples the transcription, 3′‐end formation and nuclear export of mRNAs. In this study, we report that crucial factors for mRNA processing, such as XRN2, DDX5/DDX17 and CstF64, are copurified with human THO (hTHO). Using chromatin immunoprecipitation, we found increased cross‐linking of XRN2 and CstF64 to the RNA polymerase II (RNAP II) pause site of the HSPA1A gene upon down‐regulation of THOC5, a metazoan‐specific component of hTHO. As observed in THOC5‐depleted cells, knockdown of XRN2 blocked HSP70 transcript release and increased the amount of CstF64 at the pause site. In addition, our data indicate that DDX5/DDX17 is also required for HSP70 transcript release. As the degradation of read‐through transcripts, but not cleavage at polyadenylation sites per se, was hindered upon THOC5 or DDX5/DDX17 down‐regulation, these factors appear to influence transcriptional termination. Interestingly, over‐expression of RNase H suppressed the accumulation of HSP70 transcripts in nuclear foci in THOC5‐ or DDX5/DDX17‐depleted cells. Thus, we propose a model in which hTHO, along with DDX5/DDX17, restricts the formation of R‐loops, thereby facilitating the XRN2‐mediated transcriptional termination and release of the mature transcript from the HSPA1A locus.

show abstract

ALYREF mainly binds to the 5′ and the 3′ regions of the mRNA in vivo

Cited by 95 publications

References 49 publications

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins

ALYREF links 3′‐end processing to nuclear export of non‐polyadenylated mRNA s

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

Contact Info

Product

Resources

About