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Nucleic Acid Structure01:25

Nucleic Acid Structure

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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Structural basis for Gemin5 decamer-mediated mRNA binding.

Qiong Guo1, Shidong Zhao1, Rosario Francisco-Velilla2

  • 1MOE Key Laboratory for Cellular Dynamics, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230027, Hefei, China.

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|September 2, 2022
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Gemin5

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Gemin5 is an RNA-binding protein within the Survival Motor Neuron (SMN) complex.
  • It delivers small nuclear RNAs (snRNAs) to the Sm complex via its N-terminal WD40 domain.
  • The C-terminal region of Gemin5 regulates RNA translation by binding viral and cellular mRNAs.

Purpose of the Study:

  • To determine the three-dimensional structure of the Gemin5 C-terminal region.
  • To investigate the role of its architecture in RNA binding and translation regulation.
  • To elucidate Gemin5's SMN complex-independent functions.

Main Methods:

  • X-ray crystallography to determine the 3D structure of the Gemin5 C-terminal region.
  • Mutagenesis studies to assess the importance of the pentamer/decamer architecture.
  • RNA-binding assays to evaluate ligand interactions.

Main Results:

  • The Gemin5 C-terminal region forms a homodecamer architecture (dimer of pentamers).
  • The intact pentamer/decamer structure is essential for binding RNA ligands.
  • This architecture is critical for Gemin5's regulation of mRNA translation.

Conclusions:

  • Gemin5's high-order pentameric assembly facilitates coordinated RNA ligand binding.
  • A model for Gemin5's regulatory role in selective RNA binding and translation is proposed.
  • This study provides insights into Gemin5's functions independent of the SMN complex.