Large scale RNA-binding proteins/LncRNAs interaction analysis to uncover lncRNA nuclear localization mechanisms

Huang, Youhua; Qiao, Yulong; Zhao, Yu; Li, Yuying; Yuan, Jie; Zhou, Jiajian; Sun, Hao; Wang, Huating

doi:10.1093/bib/bbab195

Cited by 22 publications

(18 citation statements)

References 67 publications

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“…In addition to its implication in chromatin structure, SAF-A is known to affect gene expression by modulating mRNA splicing, mRNA stability and mRNA localisation (Huang et al, 2021;Xiao et al, 2012;Ye et al, 2015;Yugami et al, 2007). We found a slight reduction in protein levels of FLAG-ORC1 and CDT1 (Fig S4) that may contribute to the reduced licensing in cells depleted for SAF-A.…”

Section: Discussionmentioning

confidence: 53%

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SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

Connolly

Takahashi

Miura

et al. 2022

Journal of Cell Science

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The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks also progress less consistently in cells depleted for SAF-A, contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed two distinct effects of SAF-A depletion: first, the boundaries between early- and late-replicating domains become more blurred; and second, SAF-A depletion causes replication timing changes that tend to bring regions of discordant domain compartmentalisation and replication timing into concordance. Associated with these defects, SAF-A-depleted cells show elevated -H2AX formation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.

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Section: Discussionmentioning

confidence: 53%

“…Although SAF-A promotes open chromatin, depletion of SAF-A has fairly minor effects on transcription (Nozawa et al, 2017). SAF-A is however reported to be implicated in alternative splicing (Xiao et al, 2012;Ye et al, 2015), mRNA stability (Yugami et al, 2007) and nuclear retention of mRNA (Huang et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

Connolly

Takahashi

Miura

et al. 2022

Journal of Cell Science

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“…Similarly, lncRNAs could act in an architectural manner to locate SAFBs to DNA-related tasks. In fact, lncRNA-binding has been shown for SAFBs in the most recent past [20,73].…”

Section: Discussionmentioning

confidence: 99%

Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein

Korn

Ehr

Dhamotharan

et al. 2022

Preprint

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The family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing, and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately-100-kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA- and RNA-binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerise, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species.

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“…Cell fractionation. Cell fractionation protocol was modified based on previous protocol 42 . C2C12 or SCs were collected in cold PBS, washed once and then incubated in buffer A (HEPES-KOH 50 mM pH 7.5, 10 mM KCl, 350 mM sucrose, 1 mM EDTA, 1 mM DTT, 0.1% Triton X-100) for 5 min on ice and then homogenized with a T 10 basic ULTRA-TURRAX® homogenizer at 4 th gear for 1min.…”

Section: Methodsmentioning

confidence: 99%

Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export

Qiao

Sun

Chen

et al. 2022

Preprint

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Skeletal muscle stem cells (also known as satellite cells, SCs) are essential for muscle regeneration and the regenerative activities of SCs are intrinsically governed by gene regulatory mechanisms but the post-transcriptional regulation in SCs remains largely unknown. N(6)-methyladenosine (m6A) modification of RNAs is the most pervasive and highly conserved RNA modification in eukaryotic cells and exerts powerful impact on almost all aspects of mRNA processing which is mainly endowed by its binding with m6A reader proteins. Here in this study, we investigate the previously uncharacterized regulatory roles of YTHDC1, a m6A reader in SCs. Our results demonstrate YTHDC1 is an essential regulator of SC activation and proliferation upon acute injury induced muscle regeneration. The induction of YTHDC1 is indispensable for SC activation and proliferation thus inducible YTHDC1 depletion almost abolishes SC regenerative capacity. Mechanistically, transcriptome-wide profiling using LACE-seq in both SCs and C2C12 myoblasts identifies m6A mediated binding targets of YTHDC1. Next, splicing analysis defines splicing mRNA targets of m6A-YTHDC1. Furthermore, nuclear export analysis also leads to identification of potential mRNA export targets of m6A-YTHDC1 in SCs and C2C12 myoblasts and interestingly some mRNAs can be regulated at both splicing and export levels. Lastly, we map YTHDC1 interacting protein partners in myoblasts and unveil a myriad of factors governing mRNA splicing, nuclear export and transcription, among which hnRNPG appears to be a bona fide interacting partner of YTHDC1. Altogether, our findings uncover YTHDC1 as an essential factor controlling SC regenerative ability through multi-faceted gene regulatory mechanisms in myoblast cells.

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Large scale RNA-binding proteins/LncRNAs interaction analysis to uncover lncRNA nuclear localization mechanisms

Cited by 22 publications

References 67 publications

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein

Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export

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