diff --git a/package/CHANGELOG b/package/CHANGELOG
index c6d2f3f4b3b..b87116b2940 100644
--- a/package/CHANGELOG
+++ b/package/CHANGELOG
@@ -19,6 +19,7 @@ The rules for this file:
  * 2.8.0
 
 Fixes
+ * Fix bug in PCA preventing use of `frames=...` syntax (PR #4423)
  * Fix `analysis/diffusionmap.py` iteration through trajectory to iteration
    over `self._sliced_trajectory`, hence supporting
    `DistanceMatrix.run(frames=...)` (PR #4433)
diff --git a/package/MDAnalysis/analysis/pca.py b/package/MDAnalysis/analysis/pca.py
index cad6946b2dc..4ed5486e4c6 100644
--- a/package/MDAnalysis/analysis/pca.py
+++ b/package/MDAnalysis/analysis/pca.py
@@ -142,7 +142,8 @@ class PCA(AnalysisBase):
     generates the principal components of the backbone of the atomgroup and
     then transforms those atomgroup coordinates by the direction of those
     variances. Please refer to the :ref:`PCA-tutorial` for more detailed
-    instructions.
+    instructions. When using mean selections, the first frame of the selected 
+    trajectory slice is used as a reference.
 
     Parameters
     ----------
@@ -230,6 +231,12 @@ class PCA(AnalysisBase):
        ``mean`` input now accepts coordinate arrays instead of atomgroup.
        :attr:`p_components`, :attr:`variance` and :attr:`cumulated_variance`
        are now stored in a :class:`MDAnalysis.analysis.base.Results` instance.
+    .. versionchanged:: 2.8.0
+       ``self.run()`` can now appropriately use ``frames`` parameter (bug
+       described by #4425 and fixed by #4423). Previously, behaviour was to
+       manually iterate through ``self._trajectory``, which would
+       incorrectly handle cases where the ``frame`` argument
+       was passed.
     """
 
     def __init__(self, universe, select='all', align=False, mean=None,
@@ -247,7 +254,7 @@ def __init__(self, universe, select='all', align=False, mean=None,
 
     def _prepare(self):
         # access start index
-        self._u.trajectory[self.start]
+        self._sliced_trajectory[0]
         # reference will be start index
         self._reference = self._u.select_atoms(self._select)
         self._atoms = self._u.select_atoms(self._select)
@@ -275,7 +282,7 @@ def _prepare(self):
         self._ref_atom_positions -= self._ref_cog
 
         if self._calc_mean:
-            for ts in ProgressBar(self._u.trajectory[self.start:self.stop:self.step],
+            for ts in ProgressBar(self._sliced_trajectory,
                                   verbose=self._verbose, desc="Mean Calculation"):
                 if self.align:
                     mobile_cog = self._atoms.center_of_geometry()
diff --git a/testsuite/MDAnalysisTests/analysis/test_pca.py b/testsuite/MDAnalysisTests/analysis/test_pca.py
index e157bee994e..c72971c30ed 100644
--- a/testsuite/MDAnalysisTests/analysis/test_pca.py
+++ b/testsuite/MDAnalysisTests/analysis/test_pca.py
@@ -133,6 +133,12 @@ def test_no_frames(u):
         PCA(u, select=SELECTION).run(stop=1)
 
 
+def test_can_run_frames(u):
+    atoms = u.select_atoms(SELECTION)
+    u.transfer_to_memory()
+    PCA(u, select=SELECTION, mean=None).run(frames=[0, 1])
+
+
 def test_transform(pca, u):
     ag = u.select_atoms(SELECTION)
     pca_space = pca.transform(ag, n_components=1)