Distinct Functions of the Tor1 and Tor2 Kinases in Regulation of the Ribosomal Protein Gene Expression via TORC1, Not

Amala Kaja1, Bhawana Uprety1, Pritam Chakraborty1

  • 1Division of Biochemistry and Molecular Biology, Department of Biomedical Sciences, Southern Illinois University School of Medicine, Carbondale, Illinois, USA.

PubMed

Insights

Target of rapamycin (TOR) regulates ribosomal protein gene expression. Genetic analysis reveals Tor1 and Tor2 act redundantly via TORC1, not TORC2, for pre-initiation complex formation and transcription.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The serine/threonine kinase, target of rapamycin (TOR), is crucial for cell growth and metabolism.
  • TOR functions in two distinct complexes, TORC1 and TORC2, with partially overlapping components.
  • Pharmacological inhibition of TOR by rapamycin affects pre-initiation complex (PIC) formation and ribosomal protein gene transcription.

Purpose of the Study:

  • To genetically elucidate the distinct roles of Tor1, Tor2, TORC1, and TORC2 in regulating ribosomal protein gene expression.
  • To investigate the involvement of TOR complexes in pre-initiation complex (PIC) formation and gene transcription.

Main Methods:

  • Gene knockout (null mutation) of TOR1.
  • Conditional depletion of TOR1 and TOR2 expression.
  • Utilizing TORC2-specific tor2-tsA and TORC1/TORC2-specific tor2-tsC conditional mutants.
  • Assessing pre-initiation complex (PIC) formation and transcription of ribosomal protein genes.

Main Results:

  • Null mutation or depletion of TOR1 does not affect PIC formation or transcription of ribosomal protein genes.
  • TORC2 is dispensable for ribosomal protein gene expression, as demonstrated by tor2-tsA mutants and TOR2 depletion.
  • Combined genetic inactivation of TOR1 and TOR2 (via tor1 null and tor2-tsC mutation) impairs PIC formation and reduces ribosomal protein gene transcription.
  • Tor1 and Tor2 exhibit redundant roles in PIC formation and transcription via TORC1.

Conclusions:

  • TORC2 is not required for ribosomal protein gene expression.
  • Tor1 and Tor2 function redundantly through TORC1 to regulate PIC formation and transcription of ribosomal protein genes.
  • Distinct genetic roles of Tor1 and Tor2 in ribosomal protein gene expression are mediated by TORC1.

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