RNA Detection

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  1. Resuspend beads in 60μL RLT Buffer (3original sample
    volume).

  2. Transfer beads in RLT to 20μL RNA sample and mix well.

  3. Add 120μL of 100% ethanol (6original sample volume).
    Wait for 2 min for sample to bind beads.

  4. Wash beads two times with 150μL of 70% ethanol.

  5. Remove supernatant and allow to air-dry for approximately
    5 min.

  6. Elute RNA in water or desired buffer. In this case, elute RNA
    samples by adding 26μLof1TURBO DNase Buffer (dilute
    from 10stock supplied by manufacturer).

  7. Leave beads in tube. Perform DNase treatment to remove
    background DNA by adding 1μL of murine RNase inhibitor
    and 3 μL of TURBO DNase to each sample (30μL total
    reaction volume). Incubate for 20 min at 37C.

  8. Perform a second SILANE cleanup using beads already in the
    tube:

  9. Add 90μL RLT Buffer to each 30μL sample.

  10. Add 180μL of 100% ethanol and mix well.

  11. Wait 2 min for sample to bind beads.

  12. Wash beads two times with 70% ethanol.

  13. Remove supernatant and allow beads to air dry approximately
    5 min.

  14. Elute in 10μL of UltraPure water.

  15. Analyze RNA samples using Agilent Bioanalyzer or by RT-
    qPCR (seeNote 9).


3.9 Mass
Spectrometry of
Captured Proteins


3.9.1 Protein
Precipitation



  1. Add 10% final concentration of TCA to protein elution sample.
    Incubate at 4C overnight.

  2. Centrifuge at 16,000gfor 30 min to pellet protein.

  3. Remove supernatant and replace with 1 mL of cold acetone.

  4. Centrifuge at 16,000gfor 15 min.

  5. Remove supernatant and allow pellet to dry in open tube in
    fume hood or on bench. Store protein elution samples at
     20 C.


3.9.2 In-Solution Digest
of Protein Samples for
Mass Spectrometry



  1. Resuspend protein elution sample in 40μL of freshly prepared
    8 M urea dissolved in 100 mM Tris–HCl pH 8.5.

  2. Add 3 mM TCEP and incubate 20 min at room temperature.

  3. Add 11 mM freshly prepared iodoacetamide and incubate for
    15 min at room temperature in the dark.


Identification of Direct RNA Binding Proteins Using RAP-MS 483
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