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<p>PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including <i>gld-1</i>. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses <i>gld-1</i> via a pair of adjacent FBF binding elements (FBEs) in its 3′UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the <i>gld-1</i> FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discoveries of the LST-1–FBF-2 ternary complex, the <i>gld-1</i> adjacent FBEs, and their in vivo significance predict an expanded regulatory repertoire of different assemblies of PUF-partner-RNA higher order complexes in nematode GSCs. This also suggests analogous PUF controls may await discovery in other biological contexts and organisms.</p>

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A higher order PUF complex is central to regulation of C. elegans germline stem cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月2日

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  • Chen Qiu,
  • Sarah L. Crittenden,
  • Brian H. Carrick,
  • Lucas B. Dillard,
  • Stephany J. Costa Dos Santos,
  • Venkata P. Dandey,
  • Robert C. Dutcher,
  • Elizabeth G. Viverette,
  • Robert N. Wine,
  • Jennifer Woodworth,
  • Zachary T. Campbell,
  • Marvin Wickens,
  • Mario J. Borgnia,
  • Judith Kimble,
  • Traci M. Tanaka Hall

摘要

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3′UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discoveries of the LST-1–FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predict an expanded regulatory repertoire of different assemblies of PUF-partner-RNA higher order complexes in nematode GSCs. This also suggests analogous PUF controls may await discovery in other biological contexts and organisms.