5'-UTR mediated translational control of splicing assembly factor RNP-4F expression during development of the Drosophila central nervous system

Gene. 2013 Oct 10;528(2):154-62. doi: 10.1016/j.gene.2013.07.027. Epub 2013 Jul 25.

Abstract

Drosophila RNP-4F is a highly conserved protein from yeast to human and functions as a spliceosome assembly factor during pre-mRNA splicing. Two major developmentally regulated rnp-4f mRNA isoforms have been described during fly development, designated "long" and "short," differing by a 177-nt tract in the 5'-UTR. This region potentially folds into a single long stable stem-loop by pairing of intron 0 and part of exon 2. Since the coding potential for the two isoforms is identical, the interesting question arises as to the functional significance of this evolutionarily-conserved 5'-UTR feature. Here we describe the effects of wild-type and mutated stem-loop on modulation of rnp-4f gene expression in embryos using a GFP reporter assay. In this work, a new GFP expression vector designated pUAS-Neostinger was constructed. The UAS-GAL4 system was utilized to trigger GFP expression using tissue-specific promoter driver fly lines. Fluorescence microscopy visualization, Western blotting and real-time qRT-PÇR were used to study and quantify GFP reporter protein and mRNA levels. A significant increase in GFP reporter protein expression due to presence of the wild-type stem-loop sequence/structure was unexpectedly observed with no concomitant increase in GFP reporter mRNA levels, showing that the 177-nt region enhancement acts posttranscriptionally. The effects of potential cis-acting elements within the stem-loop were evaluated using the reporter assay in two mutant constructs. Results of GFP reporter over-expression show that RNP-4F translational regulation is highly sensitive in the developing fly central nervous system. The potential molecular mechanism behind the observed translational enhancement is discussed.

Keywords: 3′-UTR; 3′-untranslated mRNA region; 5′-UTR; 5′-untranslated mRNA region; Alternative splicing; CNS; DNA complementary to RNA; Drosophila adenosine deaminase acting on RNA; GFP; GFP reporter; IRES; PCR; Posttranscriptional regulation; RNP-4F; RT-PCR; U-series small nuclear ribonucleoprotein; U-snRNP; base pair; bp; cDNA; central nervous system; dADAR; green fluorescent protein; internal ribosomal entry site; mRNA; messenger RNA; nt; nucleotide; polymerase chain reaction; reverse transcriptase-polymerase chain reaction; ribonucleoprotein encoded by rnp-4f gene in polytene band 4F; rnp-4f gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Base Sequence
  • Central Nervous System / growth & development*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Inverted Repeat Sequences
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Protein Biosynthesis*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / metabolism

Substances

  • 5' Untranslated Regions
  • Drosophila Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA-binding protein 4F, Drosophila
  • Ribonucleoproteins
  • Green Fluorescent Proteins